nancy and occur in up to 50% of pregnant women'. Hyperemzesis gravidarum is ... severe nausea and vomiting complicating pregnancy. .... in molar pregnancy.
Journal of the Royal Society of Medicine Volume 79 October 1986
Discussion
Neuroblastomas generally arise from the adrenal medulla and the sympathetic nervous chain. Approximately 65% of the tumours are located in the abdomen and 35% in other sites, often the sympathetic chain in the thorax'. The tumours have been described in several unusual sites including the bladder2, sciatic nerve3, jaw, neck and nasopharynx4. Neuroblastomas of the small intestine have only been reported twice before. Ritter in 19255 described two cases in adults aged 55 and 64. One of these patients had a very large tumour incorporating the upper part of the mesentery and several loops of jejeunum and only apparently arose from the bowel wall. In the second patient described, the histology of the small bowel tumour was relatively benign; the author commented on the atypical appearance and a diagnosis of neuroblastoma was not definitely established. We believe that the tumour in our patient arose primarily from the autonomic nerve cells in the myenteric plexus of Auerbach. However, it is conceivable that this was an isolated metastasis from a primary tumour which had undergone spontaneous regression. This phenomenon is largely confined to children under the age of 2 years6. Some tumours regress as a result of necrosis and others are thought to mature to become ganglioneuromas over a period of years. Willis7 thought that this was more likely to occur in girls. Gastrointestinal ganglioneuromas have been well described. Dahl et al.' reviewed 11 cases; of these 2 were situated in the terminal ileum, 2 in the stomach, one in the duodenum, 5 in the appendix and 2 involved the colon. The frequency of regression and maturation is variously estimated to be 1-8%'. The maturation of an extra-adrenal neuroblastoma was described by Haber and
613
L Berry of the Department of Morbid Anatomy, The London Hospital, for reviewing the histology.
References 1 Koop RC, Hernandez JR. Neuroblastoma: Experience with 100 cases in children. Surgery 1964;56:726-33 2 Harvey DF, Tennant R. Primary neurogenic sarcoma of the bladder in an infant one month of age. Am J Pathol 1934;10:125-8 3 Nesbitt KA, Vidone RA. Primitive neuroectodermal tumour (neuroblastoma) arising in sciatic nerve of child. Cancer 1976;37:1562-70 4 Hope-Stone HF. Extra-adrenal neuroblastoma. Br J Surg 1961;48:424-9 5 Ritter SA. Neuroblastoma of the intestine. Am JPathol 1925;1:519-27 6 Anonymous. Neuroblastoma. Br Med J 1968;iii:690-1 7 Willis RA. The pathology ofthe tumours of children. In: Cameron R, Payling-Wright G, eds. Pathological monographs, No. 2. Edinburgh and London: Oliver and Boyd, 1962:9 8 Dahl EV, Waugh JM, Dahlin DC. Gastrointestinal ganglioneuromas: Brief review with report of a duodenal ganglioneuroma. Am JPathol 1957;2:953-61 9 Haber SL, Bennington JL. Maturation of congenital extra-adrenal neuroblastoma. Arch Pathol 1963;76:121-5 10 Miller RW. Relation between cancer and congenital defects in man. NEngi JMed 1966;275:87-93 11 Chatten J, Voorhess ML. Familial neuroblastoma: Report of a kindred with multiple disorders, including neuroblastomas in four siblings. N Engi J Med 1967;277:1230-5 12 Kinnier Wilson LM, Draper GJ. Neuroblastoma, its natural history and prognosis: A study of 487 cases. Br Med J 1974;iii:301-7
(Accepted 7 January 1986. Corresponding to HB at The Rayne Institute, London WC1)
Bennington'.
We also considered the possibility that this woman's tumour was a metastatic lesion from a fetal primary tumour. However, there was no evidence of neuroblastoma in the infant, nor in the placenta. The normal hydroxymandelic acid levels and the return of the blood pressure to normal after the caesarean section, despite incomplete removal of the tumour, indicate that the lesion was not functionally active. Friedreich's ataxia is a hereditary disease characterized by degeneration ofthe spinocerebellar tracts, posterior columns and the pyramidal tracts. There has been no previous reported association with neuroblastoma, although patients with this hereditary ataxia do have an increased incidence of visceral carcinoma in later life. Miller'0 failed to show an increased incidence of congenital and hereditary problems in patients with neuroblastoma. However, Chatten and Voorhess " reported a family in which 4 siblings had neuroblastoma, one had long segment Hirschprung's disease and 2 had a patent ductus arteriosus. Neuroblastoma is a not uncommon tumour of children. Kinnier Wilson and Draper'2 found that 41% of patients were under 2 years of age and 91% below 10 years. It is unusual to find a patient over 14. Several features of our patient's problem are unique and serve to illustrate the protean nature of malignant neuroblastoma.
Acknowkedgments:
We thank Mr R Downie, Consultant Surgeon, for permission to report this case and Professor C
Transient hyperthyroidism in hyperemesis gravidarum
T T H Lao MRCOG R K H Chin MRCOG C S Cockram MRCP N S Panesar PhD Departments of Obstetrics and Gynaecology, Medicine and Chemical Pathology, Prince of Wales Hospital, Hong Kong Keywords: hyperemesis gravidarum, transient hyperthyroidism, carbimazole treatment
Nausea and vomiting are common symptoms in pregnancy and occur in up to 50% of pregnant women'. Hyperemzesis gravidarum is, however, relatively rare and may sometimes be associated with hyperthyroidism2'3. Transient hyperthyroxinaemia in association with hyperemesis gravidarum has also been described4. We have recently managed a patient with relapsing hyperemesis and disordered thyroid function in whom a short course of carbimazole led to clinical remission of the hyperemesis as well as reversal of the hyperthyroxinaemia.
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Journal of the Royal Society of Medicine Volume 79 October 1986 Case
report
A 28-year-old Chinese shop assistant developed severe nausea and vomiting complicating pregnancy. This pregnancy, her first after two years of marriage, was clomiphene-induced. On admission she was dehydrated, ketonuric and hypokalaemic. Ultrasound scanning confirmed a singleton pregnancy at a maturity of 12 weeks. Her symptoms initially improved following antiemetic therapy and intravenous fluid replacement. Subsequently, she required repeated admissions with relapsing hyperemesis (Table 1). On the third admission, a persisting tachycardia of 120/minute was noted despite rehydration. Her body weight fell from 54.6 kg before pregnancy to 49.7 kg. She had a small goitre and serum thyroxine was elevated at 356 nmol/l. No overt signs of thyrotoxicosis were found at this stage. On the fourth admission, her serum thyroxine had fallen to 177 nmol/l. Her serum calcium was normal. On the sixth admission, the vomiting was severe that she required parenteral nutritional support with Intralipid, Vamin G and vitamin B complex. Parenteral nutrition was again required on her next two admissions. On the eighth admission she had a tachycardia of up to 140/minute, a sleeping pulse of 80-90/minute and lid lag. The thyroid gland was diffusely enlarged, a bruit was detected and an adenomatous nodule was found in the right lower lobe by ultrasound scanning. Thyroid function tests showed markedly elevated values with a serum total thyroxine (T4) of 484 nmol/l and tri-iodothyronine (T3) 9.0 nmol/l (Figure 1). The free T4 and free T3 were 52.5 pmol/l and 29.0 pmol/l respectively. However, the red blood cell zinc level was normal. The thyroxine-binding-globulin (TBG) level was 29.1 mg/l and human chorionic gonadotrophin (HCG) level was 112 000 ul/l. There was no increase in the level of thyroid-stimulating hormone (TSH) in response to injection of thyrotrophinreleasing hormone (TRH). In view of these findings, carbimazole 15mg/day was started at 284 weeks, with marked symptomatic improvement. During this admission up to the day of starting carbimazole, she gained 3.6 kg. When she went home four days later, she gained a further 1.3 kg without nutritional so
support.
Subsequently at follow up, she admitted that she had stopped taking carbimazole after two weeks because she felt better. As there was satisfactory weight gain, carbimazole was not recommenced. At 34 weeks she went into spontaneous labour and delivered a healthy daughter weighing 2.7 kg. The assessed maturity was 35 weeks and there were no neonatal complications. The postnatal course was uneventful and both the postpartum thyroid function tests and the thyroid size have returned to normal. Discussion Nausea and vomiting are common symptoms of uncomplicated early pregnancy. Occasionally, however, an underlying cause may be found. Metabolic disorders, for example hyperthyroidism2"3, can present as hyperemesis gravidarum. If the underlying disorder is unrecognized, thyrotoxic crisis can occur2'5 with very serious consequences, whereas prompt treatment with antithyroid drugs is highly effective. Unlike many patients with hyperemesis who improve with advancing gestation, our patient had persistent symptoms and weight loss with increasing severity towards the end ofthe second trimester. Her serum T4 and T3 fluctuated but changed in parallel to the severity of her symptoms (Figure 1). Both her total and free T4 and T3 levels were greatly elevated suggesting hyperthyroidism. In addition, the TSH response to TRH was absent, as reported for thyrotoxicosis in pregnancy3. This was unlike the situation in hyperemetic and normal pregnant women6. Antithyroid therapy was therefore commenced at 28 weeks. The response was gratifying, with an apparent remission in the hyperthyroidism and good control of symptoms. Despite the short course of therapy, there was no further evidence of hyperthyroidism. Abnormal thyroid function is a recognized feature in some patients with hyperemesis gravidarum. There may be elevation of the serum protein-bound iodine (TBI) and impaired T3 suppression7. Furthermore, transient hyperthyroxinaemia may occur in hyperemesis gravidarum, with raised free thyroxine and free tri-iodothyronine indices, and no TSH response to injection of TRH'.
Table 1. Admission summary
Admission episode
Maturity ultrasound (weeks) Hospital stay
1
2
3
4
5
6
7
8
9
12.5
14.5
16
17.5
20
21.5
24
26
34
5
5
5
4
6
4
5
27
4
49.7
46.5 46.0
48.5 -
45.3 48.3
46.0 48.5
Pyrental
-
(days) Body weight (kg): On admission On discharge Remarks
OGTT normal
48.2 48.7 Diarrhoea
Vomited ascaris
pamoate and
pyridoxine given
Started parenteral nutrition
46.0 50.9
58.2
Haematemesis, Labour ? toxic nodule. Carbimazole 15 mg/day
started
Note: In all admissions except the last, the patient had ketonuria, hypokalaemia, clinical dehydration with raised haematocrit (40%). In four admissions, hepatic enzyme (SGPT) was elevated.
Journal of the Royal Society of Medicine Volume 79 October 1986 a
~~~~~~~~HCG ---~~~ ~~TSHE
X -j
C~~
~
~~~~M
40I
'
12
-
400T8
F 100-
- 32
o 81 9
u ~ Tr~~ 300 6.
11F
.2 .
--
h ~~~~~~~pru 4
20 j- 00
2
0
0
12 141 16 18 20
2'2 2'4
26 28
Gestation (wks)
3'0
32 34 post pru
Figure 1. Thyroid hormones and HCG changes throughout pregnancy In our patient, an apparent association was noted between the rise and fall of the T4, T3 and HCG levels (Figure 1). Although the role of HCG in causing hyperemesis gravidarum in normal and molar pregnancy has been disputed8, HCG or a closely related molecular variant could be responsible for raised serum total T4 levels9 and severe hyperthyroidism'0 in molar pregnancy. We suspect that in this patient, intrinsic TSH-like activity associated with HCG may have been responsible for the transient hyperthyroxinaemia which in turn suppressed the TSH response to TRH stimulation. A recent report of recurrent pregnancy-induced thyrotoxicosis presenting as hyperemesis gravidarum provides further possible evidence for the thyroid-stimulating action of HCG". A similar mechanism has been suggested as an explanation for the transient relapse in early pregnancy of some patients with known Graves' disease but in remission12. Bouillon et al.4 reported that treatment with antithyroid drugs did not modify the clinical course and had no effect on the outcome of the pregnancy. While this may be generally true, we feel that in those patients in whom the abnormality persists or worsens as pregnancy progresses, treatment with antithyroid drugs may rapidly reverse the hyperthyroxinaemia and produce resolution of the hyperemesis. Our experience, in agreement with the report of Jeffcoate and Bain", suggests that a short course only is required and that the antithyroid drugs do not need to be continued once recovery has occurred.
References 1 Fairweather DVI. Nausea and vomiting in pregnancy. Am JObstet Gyneecol 1968;102:135-75 2 Valentine BH, Jones C, Tyack AJ. Hyperemesis gravidarum due to thyrotoxicosis. Postgrad Med J 1980;56:746-7 3 Dozeman R, Kaiser FE, Cass 0, Pries J. Hyperthyroidism appearing as hyperemesis gravidarum. Arch Intern Med 1983;143:2202-3
615
4 Bouillon R, Naesens M, Van Aseche FA, et al. Thyroid function in patients with hyperemesis gravidarum. Am JObtet Gynecol 1982;143:922-6 5 Menon V, McDougall WW, Leatherdale BA. Thyrotoxic crisis following eclampsia and induction of labour. Postgrad Med J1g82;58:286-7 6 Ylikorkala 0, Kaupilla A, Haapalahti J. Follicle stimulating hormone, thyrotrophin, human growth hormone and prolactin in hyperemesis gravidarum. Br J Obstet Gynaecol 1976;83:528-33 7 Bruun T, Kristoffersen K. Thyroid function during pregnancy with special reference to hydatidiform mole and hyperemesis. Acta Endocrinol 1978;88:383-9 8 Soules MR, Hughes CL, Garcia JA, et aL Nausea and vomiting of pregnancy: Role of human chorionic gonadotrophin and 17-hydcroxyprogesterone. Obstet Gynecol 1980;55:696-700 9 Amir SM, Osathanonha R, Berkowitz RS, Goldstein DP. Human chorionic gonadotrophin and thyroid function in patients with hydatidiform mole. Am J Obstet Gynecol 1984;150:723-8 10 Hershman JM, Higgins HP. Hydatidiform mole - a cause of clinical hyperthyroidism. Report of two cases with evidence that the molar tissue secreted a thyroid stimulator. NEngl JMed 1971;284:573-7 11 Jeffcoate WJ, Bain C. Recurrent pregnancy - induced throtoxicosis presenting as hyperemesis gravidarum. Case report. Br J Obstet Gynaecol 1985;92:413-15 12 Amino N, Tanizawa 0, Mori H, et al. Aggravation of Thyrotoxicosis in early pregnancy and after delivery in Graves' disease. J Clin Endocrinol Metab
1982;65:108-12 (Accepted 10 January 1986)
Association of infective endocarditis with gastric carcinoma
D J Seddon MA MRCP London Ell
Whipps Cross Hospital,
Keywords: endocarditis, infective; carcinoma, gastric
Infective endocarditis, in particular due to Streptococcus bovis, has been reported as having a possibly causal association with carcinoma of the colon'. A case is now reported in which infective endocarditis preceded the diagnosis of a carcinoma of the stomach. Case report A 48-year-old woman presented with a one-week history of fever and malaise, together with a shorter period of unrelenting sharp right flank pain. She was receiving treatment for hypertension, and 4 years previously had had radical surgery and radiotherapy for carcinoma of the corpus uteri. There was no history suggestive of either previous rheumatic fever or rheumatic heart disease. On admission, she was febrile with a temperature of 38°C and manifested extreme tenderness in the right renal angle. There were no abnormal cardiac signs. Urinalysis revealed haematuria only and
0141-0768/86/ 010615-02/$02.00/0 o 1986
The Royal Society of Medicine
