JOURNAL OF THE ROYAL SOCIETY OF MEDICINE. Volume 89. August 1996 myopathy is not associated with raised serum creatine kinase activitiesl but ...
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myopathy is not associated with raised serum creatine kinase activitiesl but anabolic steroid misuse may be suspected in young men presenting with vague myalgic symptoms8. There was no evidence for this in case 4. Racial differences are notjust confined to the serum level of creatine kinase. Afro-Caribbeans have different reference ranges for serum amylase activity9, liver function tests10, neutrophil counts, pulmonary function tests1l and electrocardiographic findings2 (as illustrated in case 2 above). In order to avoid inconvenience to both the patient and the physician these differences need to be borne in mind: easily available laboratory tests should not be allowed to supplant a good history and examination.
3 Meltzer HY. Factors affecting serum creatine phosphokinase levels in the general population: the role of race, activity and age. Clin Chim Acta 1971 ;33: 165-72 4 Meltzer HY, Holy PA. Black-white differences in serum creatine phosphokinase activity. Clin Chim Acta 1974;54:215-24 5 Black HR, Quallich H, Gareleck CB. Racial differences in serum creatine kinase levels. AmJ Med 1986;81:479-87 6 Wong ET, Cobb C, Umehara MK et al. Heterogeneity of serum creatine kinase activity among racial and gender groups of the population. AmJ Clin Pathol 1983;79:582-6 7 Olerud JE, Homer LD, Carrol HW. Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury. Arch Intem Med 1976;136:692-7 8 Perry HM, Littlepage BNC. Misusing anabolic drugs. Take a drug history from well muscled patients. BMJ 1992;305:1241-2 9 Tsianos EB, Jalalai MT, Gowenlock AH, Braganza JM. Ethnic 'hyperamylasaemia': clarification by isoenzyme analysis. Clin Chim Acta 1982;124:13-21 10 Manolio TA, Burke GL, Savage PJ et al. Sex- and race-related differences in liver-associated serum chemistry tests in young adults in the CARDIA study. Clin Chem 1992;38:1853-9 11 Miller A. Pulmonary Function Tests. Philadelphia: W B Saunders, 1987
REFERENCES I Rosalki SB. Serum enzymes in disease of skeletal muscle. Clin Lab Med 1989;9:767-81 2 Hampton JR. The ECG in Practice. Edinburgh: Churchill Livingstone, 1992
August 1996
Delayed puberty and reversible pituitary enlargement in a girl Richard I G Holt MRCP
T D Meurig Williams MRCP
J R Soc Med 1996;89:464-466
INTRODUCTION
The combination of hyperprolactinaemia, amenorrhoea and enlargement of the pituitary in a young woman usually suggests a prolactinoma. We describe the case of a gIrl who presented with primary amenorrhoea and growth delay associated with hyperprolactinaemia and suprasellar enlargement of the pituitary, whose underlying diagnosis was not a prolactinoma as initially thought but primary hypothyroidism. CASE HISTORY
A 15-year-old girl was referred to the gynaecologists for investigation of primary amenorrhoea. She had a cyclical vaginal discharge but no definite per vaginam (PV) bleeding. She was an only child and had had a normal delivery with a birth weight of 81b 4oz (3.75 kg). Her parents were alive and Thanet District Hospital St Peters Road, Margate, Kent CT9 4AE, England
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Correspondence to: RIG Holt, Department of Medicine, King's College School of Medicine and Dentistry, Bessemer Road, London SE5 9PJ, England
well and there was no family history of endocrine disorders. On examination, she was pre-pubertal with absent pubic and axillary hair and no breast development. In addition she was below the third percentile for height. Chromosomal analysis showed she was 46XX. She had a normal pelvic ultrasound. Luteinizing hormone (LH) was 1.0 IU/l and follicle stimulating hormone (FSH) was 7.1 IU/l. However her prolactin was raised at 1858 mU/l. A skull radiograph and formal visual field testing were normal. Her delayed puberty was thought to be due to hyperprolactinaemia causing suppression of the hyperthalamo-pituitary-ovarian axis and she was started on bromocriptine 2.5mg daily. Subsequently her prolactin fell to within the normal range (449 mU/l) and she began to menstruate normally and to develop secondary sexual characteristics. However, after 6 months on bromocriptine there was no growth in stature and she was referred for further endocrine investigation. No further history was available and there was no clinical abnormality apart from
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tomography (CT) head scan showed a 1.6 cm pituitary tumour with suprasellar extension (Figure 2a). She was started on thyroxine replacement (125 /g daily) and the bromocriptine was stopped. The serum TSH fell into the normal range while serum prolactin remained normal. She continued to menstruate normally and during the subsequent 12 months grew 3.5 cm with her bone age advancing to 14 years. A repeat CT scan at this stage showed complete resolution of the pituitary 'tumour' (Figure 2b). DISCUSSION Primary hypothyroidism in adults can occasionally give rise to secondary amenorrhoea, hyperprolactinaemia and pituitary enlargementl ,2. To our knowledge this is the first case to be reported in a child in whom primary hypothyroidism caused not only growth retardation but also
her short stature. In particular she appeared euthyroid. Her breasts were now Tanner stage 4 and pubic hair stage 2. Further endocrine investigations showed the following: 9am cortisol 367nmol/l; growth hormone 12.9mU/l; insulin like growth factor-I 22.4nmol/l; LH 1.1 IU/l; FSH 4.3 UIll; thyroid stimulating hormone (TSH) greater than 50mU/l; total thyroxine 15nmol/l; thyroid microsomal antibodies positive in a high titre. Bone age was 12.5 years indicating a delay of 3.5 years (Figure 1). Her corrected height was on the twentieth centile. A computerized
primary amenorrhoea, hyperprolactinaemia and reversible suprasellar enlargement of the pituitary. Pituitary enlargement has been described in a number of primary endocrine organ failures, including Turner's syndrome, Klinefelter's syndrome and hypothyroidism. Hypothyroidism leading to pituitary enlargement with suprasellar extension was first described in 18513. This enlargement may result in chiasmal compression2 but treatment with thyroxine causes regression of these 'tumours'1. The increased pituitary size is presumably secondary to thyrotroph hyperplasia and this may eventually predispose to TSH secreting pituitary adenomas4. In addition, in experimental animals, destruction of the thyroid gland or administration of antithyroid drugs may lead to the development of TSH secreting pituitary tumours. Initially, these are dependent on maintenance of hypothyroidism and regress with thyroxine replacement but if left untreated they may become autonomous and finally non-secreting5.
(a)
(b)
Figure 1 Growth chart showing growth delay and relative bone age and catch-up growth following thyroxine therapy
Figure 2 (a) Computerized tomography scan of the pituitary showing a 1.6 cm pituitary tumour with suprasellar extension; (b) resolution of the 'tumour' with thyroxine treatment
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Hyperprolactinaemia may occur in patients presenting with primary hypothyroidism. This may be secondary to increased hypothalamic TRH release or to interruption of hypothalamic dopamine as a result of pituitary expansion. Its return to normal after bromocriptine in this case suggests that interruption of hypothalamic dopamine does indeed make a major contribution to the hyperprolactinaemia associated with primary hypothyroidism. Hypothyroidism may cause a delay in both growth and pubertal development in children. The underlying mechanisms are likely to be complex because rarely hypothyroidism is associated with raised LH levels, testicular enlargement in young boys and precocious puberty in girls. In the present case, it was notable that correction of the hyperprolactinaemia with bromocriptine allowed puberty to proceed but no linear growth occurred until the hypothyroidism was treated. This suggests that pubertal delay was an indirect effect of hypothyroidism via suppression of the hypothalamo-pituitary-ovarian axis by prolactin. In contrast, the growth delay was likely to be a direct result of low circulating thyroid hormones which was corrected only after thyroxine replacement. The diagnosis of hypothyroidism in children is notoriously difficult on clinical grounds. However, it is
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particularly important in childhood to make this diagnosis in order to maximize growth. Inappropriate treatment with bromocriptine in girls may lead to premature oestrogenization of the skeleton and early fusion of the epiphyseal plates and thereby reduce the final height. This case illustrates that thyroid status should be assessed in all patients including adolescents with amenorrhoea and hyperprolactinaemia even if they appear euthyroid. REFERENCES 1 Heyburn PJ, Gibby OM, Hourihan M, Hall R, Scanlon MF. Primary hypothyroidism presenting as amenorrhoea and galactorrhoea with hyperprolactinaemia and pituitary enlargement. BMJ 1986;292:1660 2 Lecky BRF, Williams TDM, Lightman SL, Plant GT, Stevens J. Myxoedema presenting with chiasmal compression: resolution after thyroxine replacement. Lancet 1986;i:1347-50 3 Niepke P. Enlarged Sella Due to Cretinism (hypothyroidism) (Traite du Goitre et du Crietinisme). Paris: Bailliere, 1851 4 Samaan NA, Osbourne BM, Mackay B, Leavens ME, Duello TM, Halmi NS. Endocrine and morphologic studies of pituitary adenomas secondary to primary hypothyroidism. J Clin Endocrin Metab 1977;45:903-1 1 5 Furth J, Dent NN, Burnett WT. The mechanism of induction and the characteristics of pituitary tumours induced by thyroidectomy. J Clin Endoain Metab 1955;15:81-7
(Accepted 7July 1995)
