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Diabetes Clinical Case Series, Excerpt #5, Endocrinology and Diabetes

Dec 29, 2013

Ramsi Ajjan


Iwona is a 30-year-old woman with known type 1 diabetes for 12 years. She visits her GP complaining of tiredness and weight gain. Her HbA1c levels over the past 7 years have ranged between 6.4 and 7.1%, but her most recent test showed an HbA1c of 8.3%.
What would you do at this stage?…

This is a young woman with type 1 diabetes that has been well-controlled indicating that she is a reliable and a compliant patient. Her diabetes control has deteriorated recently, which may be related to:

  • Weight gain
  • Change in the dose of insulin
  • Compliance issues
  • Problems with the injection sites (i.e. lipohypertrophy)
  • Weight gain may be due to:
    • Change in lifestyle (different diet, less exercise)
    • Endocrine problems (Cushing’s syndrome, hypothyroidism)
    • Depression (some individuals with depression tend to eat more)
  • Tiredness is a non-specific symptom (reviewed elsewhere). In this particular patient, it may simply be due to deterioration in diabetes control.

A more detailed history at this stage is essential, in particular addressing any change in diet, lifestyle or dose of insulin.

Iwona tells you that her diet has not changed but she is undertaking less exercise due to extreme fatigue. The dose of her insulin has not changed and she continues in her current job as a teacher and has no family problems or social issues of note.

How does this information help you?

  • The above suggests that Iwona has an organic cause for her tiredness that is probably not directly related to her diabetes.
  • Her symptoms should be further explored keeping in mind the association of type 1 diabetes with other endocrine autoimmune conditions such as hypothyroidism and hypoadrenalism.
  • Hypothyroidism is a common disease, particularly in type 1 diabetes and questions regarding specific symptoms of hypothyroidism (Table 9, p. 18) should be asked at this stage.
  • The possibility of hypoadrenalism (Addison’s disease) is less likely as this is usually associated with weight loss and hypoglycaemia (or reduced insulin requirements), which are not seen here.

On further questioning, Iwona tells you that her skin is getting very dry, is feeling constantly cold and her hair is becoming coarse and brittle. Also, she has had recent problems with menstrual irregularities and has been constipated.

What would you do now?

Iwona’s symptoms are consistent with hypothyroidism, and, therefore, examination of her thyroid status should be the next step (Part 1, p. 34).

On examination, Iwona indeed has dry skin and inspection of her face reveals periorbital puffiness. Her pulse is slow at 52 beats/min regular and she has slow relaxing reflexes. Neck palpation reveals no goitre.

What is your diagnosis so far and what tests would you request?

  • Iwona has classical signs of hypothyroidism (summarized in Table 9, p. 18). Therefore, the likely diagnosis is autoimmune hypothyroidism (AH), which may occur:
    • In the presence of a thyroid goitre, a goitrous form or Hashimoto’s thyroiditis
    • In the absence of a thyroid goitre, the atrophic form or primary myxoedema
  • The diagnosis can be confirmed by checking thyroid function tests (TFTs) and thyroid peroxidase (TPO) antibodies:
    • TFTs are expected to show low thyroid hormones and raised TSH
    • TPO antibodies are usually positive in patients with AH

Iwona’s tests show a FT4 of 6.1 mmol/L and TSH of 81 mIU/L with positive TPO antibodies.

How would you manage this patient now?

  • These tests are consistent with AH and the patient will need T4 replacement therapy
  • Thyroxine treatment can be started in a young patient at a full replacement dose. In the older age group, in those with cardiac problems, and in longstanding hypothyroidism, an initial small dose is advised with gradual titration to an appropriate maintenance dose
  • TSH should be rechecked around 6 weeks after starting treatment or after modifying the dose of T4
  • The maintenance dose of T4 is around 1.4 mcg/kg

Iwona tells you that she is planning a pregnancy in the next year or so.

What advice would you give her?
  • Pregnant hypothyroid women usually need a 30–50% increase of T4 dose and this should be fully explained to patients with hypothyroidism of child-bearing age
  • Iwona should inform her endocrinologist once she becomes pregnant, in order to increase the dose of T4 and make appropriate arrangements to monitor TFTs during pregnancy

Iwona’s symptoms completely disappear on 100 mcg of T4, which is further increased to 150 mcg when she becomes pregnant 9 months later. She goes through an uneventful pregnancy and the dose of T4 is decreased after delivery to 100 mcg/day. Twelve months after delivery her TFTs showed a FT4 of 18.6 pmol/L and TSH 1.2 mU/L on 100 mcg T4.

What do these results indicate?
  • The patient seems to be well replaced with thyroxine as both her FT4 and TSH are in the normal range
  • It is advisable to have the TSH between 0.2 and 2.0 mU/L in patients having thyroxine replacement therapy, which is the case in this patient

Iwona comes to see you 2 years later complaining of tiredness, muscle cramps, aches and weight gain.

What would you do?

Iwona’s TFTs should be checked as her symptoms are consistent with under-replacement with thyroxine.

Her TFTs showed:
FT4 22.1 pmol/L
TSH 15.8 mU/L
How do you explain these findings?
  • This is a relatively common finding in patients on thyroxine replacement and is usually indicative of non-compliance
  • The patient is not taking thyroxine regularly causing an elevation of TSH. However, the patient takes the thyroxine before the blood test resulting in normal FT4 but TSH remains high
    • It takes TSH a few weeks to normalize in patients having thyroxine replacement and this is why TFTs should not be repeated less than 4–6 weeks following initiation or change in treatment

Iwona admits to having some difficulties at work resulting in non-compliance. These issues are subsequently resolved and her TFTs normalize 3 months later. She comes to see you again with a skin condition, as shown in Fig. 48 (colour plate section).

What is the diagnosis?
  • Iwona’s skin shows areas of decreased pigmentation
  • The diagnosis is vitiligo

Is Iwona’s skin condition related to her thyroid disease?

  • Vitiligo is an autoimmune condition that can be associated with autoimmune disorders, particularly autoimmune thyroid disease







Ramzi Ajjan, MRCP, Med Sci, PhD, Senior Lecturer and Honorary Consultant in Diabetes and Endocrinology, Department of Health Clinician Scientist, The LIGHT Laboratories, University of Leeds, Leeds, UK

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