Ewan A. Masson

Spontaneous recovery of chemotherapy-induced primary ovarian failure: implications for management.

A 14‐year‐old female patient presented with a swelling, which was excised, over the left forearm. Histology revealed a poorly differentiated rhabdomyosarcoma and she was treated with multiple chemotherapy for 2 years, including cyclophosphamide, cisplatin and vincristine. She developed secondary amenorrhoea shortly after commencing treatment which persisted on its completion. Biochemical investigations were consistent with ovarian failure, which was assumed to be chemotherapy‐induced and permanent. She was given hormone replacement with a conjugated equine oestrogen/norgestrel combination, resulting in regular withdrawal bleeding. At 22 years of age, she presented with amenorrhoea for 3 months. Investigations revealed FSH 2.7 IU/l, LH >50 IU/l and oestradiol >1320 pmol/l. A pregnancy test was positive and subsequent ultrasound scanning confirmed the presence of a foetus of 18 weeks gestation. The patient initially considered a termination as she had been unprepared for this event but later elected to continue the pregnancy which proceeded uneventfully and resulted in the birth of a normal infant. Ovarian function should be reassessed periodically in patients with chemotherapy‐induced gonadal damage and/or the oral contraceptive pill should be used as hormone replacement unless fertility is desired.

Increased Insulin Requirement in a Patient with Type 1 Diabetes on Rifampicin

Infection may have a major effect on diabetes control, and patients with diabetes have an increased susceptibility to some infections, including tuberculosis.’ Pulmonary tuberculosis is reported to be increasing in inner city areas,2 thus more patients may be seen in diabetic clinics on anti-tuberculous chemotherapy. We report a case of a patient with Type 1 diabetes mellitus whose insulin requirements increased during rifampicin therapy for pulmonary tuberculosis. A 54-year-old woman with Type 1 diabetes, free of diabetes-related complications, was diagnosed as having pulmonary tuberculosis and commenced on triple therapy with Rifinah 300 (rifampicin 300 mg and isoniazid 150 mg) two tablets daily, and pyrazinarnide 1500 mg daily. She was maintained on a total of 36 units of human actrapid and monotard insulin on a twice daily regime which was not changed on starting anti-tuberculous chemotherapy. She was on no other medication. Two weeks later she was admitted to hospital with nausea and vomiting and a blood glucose of 28 mmol I-’, but with no evidence of ketoacidosis. Her nausea and vomiting settled after stopping the pyrazinamide, and she was discharged 5 days later on Rifinah 30, two tablets daily. Glycaemic control was only achieved after increasing her insulin to 48 units per day. During the remaining 8 months of her antituberculous chemotherapy her diabetes remained well controlled on 44-48 units of insulin per day, and her weight remained steady at 79 kg. She experienced only one or two minor hypoglycaemic episodes per month, usually precipitated by exercise. Immediately on discontinuing her anti-tuberculous chemotherapy, she developed frequent hypoglycaemic attacks; over a 2-month period her weight increased by 12 kg. These attacks persisted until her insulin was reduced to 36 units per day, the dosage preceding treatment with rifampicin. She remains well, with no evidence of recurrence, 9 months after discontinuation of her anti-tuberculous chemotherapy, and her weight i s returning to its pretreatment level. The temporal relationship between the increase in her insulin requirement on initiating treatment, and the sudden decrease on stopping treatment, suggest that her anti-tuberculous chemotherapy was responsible for the change in her diabetes control. Infection alone may affect diabetes control, and the changes of insulin dosage reported here could be accredited to the underlying disease of pulmonary tuberculosis. However, following the increase in her insulin dose, she was well throughout the remainder of her anti-tuberculous treatment. Her insulin requirement decreased sharply on stopping treatment, at a time when her tuberculosis would be considered to be cured. Therefore, it i s unlikely that tuberculous infection per se was the cause of her relative insulin-resistant state. Rifampicin is a potent hepatic enzymeinducing agent that may accelerate the metabolism of oral hypoglycaemic agents in patients with Type 2 d iabe te~ .~ However, we have been unable to find any reports of rifampicin alone affecting glycaemic control in patients with Type 1 diabetes . Rifampicin has been shown to cause early hyperglycaemia in non-diabetic patients with and without pulmonary tuberculosis, associated with enhanced insulin and C-peptide ~ecre t ion .~ No effects were seen with isoniazid, ethambutol, streptomycin, and/or para aminosalicylic acid on blood glucose, serum insulin or Cpeptide level^.^ This would suggest that the isoniazid in Rifinah taken by the patient was not responsible for the change in her insulin requirements. It i s unlikely that the pyrazinamide was responsible as there was no decrease in her insulin requirement when this was discontinued (due to nausea was still taking that the effect alone. It has been may augment and vomiting) while she rifampicin. This suggests was due to rifampicin

Isolated adrenocorticotropin deficiency presenting as primary infertility

A 31 year old female presented with primary infertility and gave a two year history of amenorrhea without symptoms or signs of endocrine dysfunction. Examination was normal and investigation showed low oestradiol and progesterone levels with decreased LH pulsatility. The cortisol responses were impaired following hypoglycaemic stress and a short synacthen test, but the cortisol response to a prolonged synacthen test was normal. An inadequate ACTH response to CRF testing confirmed the diagnosis of isolated ACTH deficiency. Hydrocortisone therapy was followed by an ovulatory menstrual cycle. Amenorrhea again ensued following the reduction of the steroid dose and normal menses resumed on normal steroid replacement therapy. Six hourly gonadotrophin pulsatility showed a significant increase in both pulse amplitude and mean LH and FSH levels following steroid treatment. Isolated ACTH deficiency is a rare but treatable cause of hypogonadism and infertility, and this case gives further insight on the role of cortisol on the hypothalamo-pituitary gonadal axis.

Effects of quinagolide (CV 205‐502), a selective D2‐agonist, on vascular reactivity in patients with a prolactin‐secreting adenoma

BACKGROUND Quinagolide (CV 205 502) Is a dopamine D2‐receptor agonist which has proved effective In the treatment of prolactinomas, reducing both serum PRL and tumour size. Some of Its D2‐receptor effects are mediated via α‐adrenoceptors, which have a major influence on the control of vascular tone. The aim of this study was to examine the influence of quinagolide on In‐vivo dorsal hand vein vascular responses to noradrenaline In patients with a prolactinoma.

d-Valine selective medium does not inhibit human fibroblast growth in vitro

Dear Editor: The purpose of this letter is to inform fellow scientists that the amino acid a-vahne (D-vat) may not be universally used for the inhibition of fibroblast proliferation in mixed human cell culture systems. Fibroblasts proliferate more rapidly than the epithelial components of explants and dispersed cell systems, resulting in rapid fibroblast overgrowth. To overcome this problem, various strategies have been employed including cell separation techniques (2), the use of agents such as genticin (5) and putrescine (8), and specific monoclonal antibodies with complement-mediated fibroblast lysis (7). It has been reported that fibroblasts lack the enzyme D-amino acid oxidase, preventing the stereoconversion of oto L-amino acids which are required for protein synthesis (3). The replacement of the essential amino acid L-val with its stereoisomer D-val in culture medium has been shown to inhibit fibroblast overgrowth from some explanted tissues in culture and has been applied to other culture systems (3,9). The failure of a commercial D-vat medium to inhibit fibroblast overgrowth in dispersed human anterior pituitary adenoma cell culture led us to reevaluate the effectiveness of D-val fibroblast inhibition in the presence and absence of fetal bovine serum (FBS). Three human fibroblast populations derived from neonatal and adult foreskin and adult pituitary adenoma were grown to confluence in Eagles minimal essential medium (MEM) (containing L-val) supplemented with 10% FBS (MEM + 10%, GIBCO, Glasgow, UK). Culture purity was determined by immunostaining for epithelial cell (cytokeratin markers, epithehal membrane antigen) and endothelial cell markers (Factor VIII-related antigen) which

Benign intracranial hypertension associated with the withdrawal of a non-ergot dopamine agonist

The cases are reported of two patients who developed benign intracranial hypertension after the withdrawal of the novel non-ergot derived dopamine agonist CV 205 502 (quinagolide).