Case Presentations in Endocrinology and Diabetes

Case presentations

Outline

Chapter 1: Case 1

Chapter 2: Case 2

Chapter 3: Case 3

Chapter 4: Case 4

Chapter 5: Case 5

Chapter 6: Case 6

Chapter 7: Case 7

Chapter 8: Case 8

Chapter 9: Case 9

Chapter 10: Case 10

Chapter 11: Case 11

Chapter 12: Case 12

Chapter 13: Case 13

Chapter 14: Case 14

Chapter 15: Case 15

Chapter 16: Case 16

Chapter 17: Case 17

Chapter 18: Case 18

Chapter 19: Case 19

Chapter 20: Case 20

Chapter 21: Case 21

Chapter 22: Case 22

Chapter 23: Case 23

Chapter 24: Case 24

Chapter 25: Case 25

Chapter 26: Case 26

Chapter 27: Case 27

Chapter 28: Case 28

Chapter 29: Case 29

Chapter 30: Case 30

Chapter 31: Case 31

Chapter 32: Case 32

Chapter 33: Case 33

Chapter 34: Case 34

Chapter 35: Case 35

Chapter 36: Case 36

Chapter 37: Case 37

Chapter 38: Case 38

Chapter 39: Case 39

Chapter 40: Case 40

Chapter 41: Case 41

Chapter 42: Case 42

Chapter 43: Case 43

Chapter 44: Case 44

Chapter 45: Case 45

Chapter 46: Case 46

Chapter 47: Case 47

Chapter 48: Case 48

Chapter 49: Case 49

Chapter 50: Case 50

Chapter 51: Case 51

Case 1

Publisher Summary

This chapter presents the details of a case, Case 1, in which a 47-year-old divorced lady was referred to the endocrine clinic by her general practitioner with a five-year history of progressive tiredness. She found it difficult to cope at her work and tended to become rather sleepy in the evening. When she awoke in the morning, she was full of energy but soon tired during the day. She also noted that she took a long time to get over colds and minor illnesses. On examination, this was a rather thin patient, weighing 47 kg, height 1.57 m. Although not clinically anemic, her skin was pale and she had no hair in the axillary or pubic areas. This patient gave a clear history that she started to develop hypopituitarism shortly after TB meningitis. However, the degree of failure and the pattern of presentation depend partly on the etiology of hypopituitarism and partly as to which anterior pituitary hormones are affected. It was likely that this patient had gonadotrophin deficient for approximately 20 years and ACTH deficient probably for at least five years as judged from her history.

A 47-year-old divorced lady was referred to the endocrine clinic by her general practitioner with a five–year history of progressive tiredness. She found it difficult to cope at her work and tended to become rather sleepy in the evening. When she awoke in the morning she was full of energy, but soon tired during the day. She also noted that she took a long time to get over colds and minor illnesses. Twenty years previously she had had tuberculous meningitis and had been treated with a full course of streptomycin, isoniazid and PAS together with intrathecal streptomycin. She recalled that for a while during the illness, she had developed marked thirst and polyuria which had been treated by injections of Pitressin. This treatment was stopped after one year and she had had no further symptoms. For the past ten years she had always had rather dry skin, which for the past five years had also remained pale. When she went on holiday, she noticed that she did not develop a good sun-tan. Her periods stopped shortly after the treatment for her tuberculosis. At about that time she got divorced. She had no children. She was currently taking no medication.

On examination this was a rather thin patient, weighing 47 kg, height 1.57 m. Although not clinically anaemic, her skin was pale and she had no hair in the axillary or pubic areas. Blood pressure was 130/80 mmHg lying, which fell to 115/70 mmHg when standing. The rest of her cardiovascular and respiratory system was quite normal.

She had no galactorrhoea but her breasts were rather atrophic. Abdominal examination was unremarkable. External genitalia showed an atrophic vulva and vagina. There were no abnormal neurological signs and her visual fields were full to confrontation. Fundoscopy was unremarkable.

Her haemoglobin was 11.7 g/dl with normal blood indices and a white cell count of 4.0 × 10⁹/l. Plasma sodium was 138 mmol/l, potassium 3.4 mmol/l and urea 4.5 mmol/l. Total serum thyroxine was 100 nmol/l with a free thyroxine index in the normal range at 97. A random cortisol performed in the clinic was 295 nmol/l but her 24-hour urine collection showed a urinary free cortisol of less than 60 nmol/24 h. Plasma 17β-oestradiol was less than 125 pmol/l and plasma progesterone was 0.8 nmol/l. She had a normal response of plasma cortisol to Synacthen with a peak level of 652 nmol/l. She was admitted for further evaluation and the results of her pituitary function tests are given in Table 1a. Chest X-ray showed that she had a calcified focus in the left upper zone. X-ray of her skull showed no abnormality and the pituitary fossa was normal in size. CT scans of the pituitary and hypothalamic area were also normal. Perimetry of visual fields showed no abnormality.

Table 1a

Results of pituitary function tests

After starting replacement therapy, her 24-hour urine output ranged between 1.6 and 1.81/24 h.

Questions

1. What biochemical evidence does this patient have of hypopituitarism and what is its likely cause?

2. What are the possible electrolyte disturbances associated with hypopituitarism?

3. What are the dangers of starting thyroxine therapy?

4. What the the indications for sex hormone replacement therapy?

Comments

This patient gives a clear history that she started to develop hypopituitarism shortly after TB meningitis. However, the degree of failure and the pattern of presentation depend partly on the aetiology of hypopituitarism and partly on which anterior pituitary hormones are affected. It is likely that this patient has been gonadotrophin deficient for approximately 20 years and ACTH deficient probably for at least five years as judged from her history.

The biochemical evidence that she has hypopituitarism rests on the results of dynamic tests of anterior pituitary function. If hypopituitarism is suspected, the dose of insulin should be 0.05 U/kg. It is essential that adequate hypoglycaemia is achieved (blood glucose <2.0 mmol/l). A normal growth hormone response is judged by values greater than 20 mU/l and the cortisol response should be greater than 600 nmol/l. It is, however, important to check that the adrenals are responsive to Synacthen prior to interpretation of the insulin stress test (plasma cortisol should rise to 600 nmol/l after 1 mg depot Synacthen). This patient’s LH and FSH responses to LHRH are totally inadequate (normal responses should show rises of approximately 10 and 5 U/l, respectively). Clearly, her TSH response to TRH is inadequate as her values remain undetectable; a normal response shows a rise of at least 2 mU/l following TRH, the peak occurring at 20 minutes. This patient therefore has growth hormone, ACTH, gonadotrophin and TSH deficiencies. It appears that her prolactin secretion is quite normal.

There are many causes of hypopituitarism but in this instance the circumstantial evidence strongly suggests that it was secondary to TB meningitis. Other causes of hypopituitarism include a variety of pituitary adenomas and secondary deposits from carcinomas, especially from the breast or lung. Occasionally, local cerebral tumours such as meningioma or glioma of the optic chiasm can cause hypopituitarism. Other infectious diseases that cause this disorder include syphilis and encephalitis. A common cause is surgical hypophysectomy for pituitary tumours; this is particularly apparent following transfrontal surgery, but is less likely with the trans-sphenoidal approach when adenomectomy is attempted with the intention of leaving normal pituitary tissue. External or interstitial irradiation to pituitary tumours may cause hypopituitarism many years after therapy. Occasionally, head trauma or hypothalamic disease such as craniopharyngioma may result in anterior pituitary deficiency. It is rare these days to have postpartum necrosis causing Sheehan’s syndrome but occasionally patients with vascular malformations or pituitary apoplexy can develop acute hypopituitarism.

It is important to emphasize that the presentation of hypopituitarism will vary with the specific hormone deficiencies that occur. Certainly, not all patients will develop panhypopituitarism and the clinician must be aware of partial pituitary deficiency.

It is not uncommon for patients with hypopituitarism to develop hyponatraemia. This is commonly due to water retention and not due to sodium loss. It is unusual for patients to develop mineralocorticoid deficiency but water diuresis is impaired by cortisol deficiency. Furthermore, there is increased vasopressin secretion in glucocorticoid deficiency. These mechanisms account for the difficulty in excreting a water load and for the hyponatraemia. It is important that the patients should be on hormonal replacement before there is formal testing for diabetes insipidus.

Adults with panhypopituitarism clearly need hormone replacement therapy but it is essential that cortisol replacement be introduced before replacement thyroxine is started. Hydrocortisone 20 mg on first rising and 10 mg mid-afternoon should be administered. If thyroxine is given before cortisol it is possible to induce adrenocortical crisis. In the elderly patient, if there is a long history of hypopituitarism it is always wise to introduce thyroxine slowly, possibly starting at a low dose of 25 μg daily and increasing to 100–150 μg over a few weeks. This is particularly important if there is any evidence of heart disease.

Steroid cards and Medic-Alert bracelets must be recommended for all patients taking long-term steroid replacement therapy. Patients should also be educated about changes in steroid dose with illness.

It is important that adult women up to the age of 45 years who show gonadotrophin deficiency should be started on replacement sex steroid therapy. Not only does that improve their atrophic genitalia and increase their sense of femininity but it will also protect their bones from osteoporosis later in life. They should receive cyclical oestrogen and progesterone therapy given in a manner to cause regular withdrawal bleeds. Some centres recommend curettage of the endometrium once every 3–5 years.

If women wish to have a pregnancy they will require cyclical treatment with HCG, Pergonal and/or highly purified human FSH. A few patients with hypogonadotrophic hypogonadism suffer from gonadotrophin releasing hormone deficiency. If these patients have otherwise normal pituitary function they may be suitable for pulsatile LHRH treatment to induce ovulation. Sex hormone replacement therapy in men who are hypogonadal is also important to restore their libido, secondary sexual characteristics and sense of well-being. It is generally recommended that they have a subcutaneous testosterone implant every 4–6 months or intramuscular testosterone at 2–4 week intervals. Such treatment, however, does not return fertility and if improvement in the spermatogenesis is required this may respond to courses of HCG and