A step towards cinacalcet testing for the diagnosis of primary hyperparathyroidism: comparison with the standardized intravenous calcium loading. A pilot study.

OBJECTIVE: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT. METHODS: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h. RESULTS: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT. CONCLUSION: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC.

Simultaneous suprasellar and pineal germ cell tumors in five late stage adolescents: endocrinological studies and prolonged follow-up.

Primary germ cell tumors (PGCT) of the central nervous system usually develop in the third ventricle area, and most frequently in the pineal region. The suprasellar region is the second preferential site for development of these tumors which are rarely simultaneously present in these two sites. We report five new cases of PGCT with pineal and suprasellar localizations, which appeared in late puberty in four boys and one girl aged 17-19 years. The clinical picture associated signs of intracranial hypertension, convergence and verticality palsies, diabetes insipidus and pituitary deficiency. Encephalic MRI revealed a double localization. Endocrine tests revealed a particular pattern associating central diabetes insipidus and a hypothalamic-pituitary disconnection syndrome. Following identification of the pathological type of lesions via a neurosurgical approach, treatment was based on a combined method using chemotherapy, radiotherapy and hormone replacement. Based on this treatment, prolonged remissions were obtained with a good quality of life.

An oestrogen-producing seminoma responsible for gynaecomastia.

In feminising testicular tumours, oestrogens can be either secreted by the tumour itself or produced by normal Leydig cells in response to paracrine and/or endocrine stimulation by hCG. Typical hormonal Leydig cell tumour patterns include: plasma oestradiol levels > 300 pmol/l on day 3 following an hCG injection, reduced plasma testosterone, and normal plasma hCG and gonadotrophin levels. Except for elevated plasma oestradiol levels, opposite results are observed in seminomas. We report a case of oestrogen-secreting seminoma mimicking a Leydig cell tumour. A 24-year-old Caucasian patient had complained of gynaecomastia for 6 months before admission. Hormonal pattern was typical of Leydig cell tumour. A 1.4 cm tumour was found in the left testis and confirmed on sonography. Considering the likely diagnosis of Leydig cell tumour, the patient was treated by tumourectomy. Surprisingly, pathological examination revealed a pure seminoma. Perifusion experiments showed that the tumour was able to secrete significant amounts of oestradiol. In addition, hCG induced a two-fold increase in oestradiol production from perifused tumour explants. Immunohistochemistry revealed that the tumour was composed of nests of seminoma cells intermingled with lymphoid infiltrates. Tumour cells also expressed aromatase, the hCG/LH receptor and the Leydig cell marker relaxin-like factor, but were betahCG-negative. These results demonstrate that a pure seminoma of the testis is able to synthesise and secrete oestrogens. They also illustrate that the body of proof favouring the diagnosis of feminising Leydig cell tumour of the testis is not rigorously specific.

Does age play a role in clinical presentation of hypothyroidism?

OBJECTIVE: To determine if aging modifies the clinical presentation of hypothyroidism. DESIGN: Comparison of 24 clinical signs of hypothyroidism between elderly patients (> or = 70 years of age) and younger patients (< or = 55 years of age). SETTING: Prospective study of patients with chemically confirmed overt hypothyroidism. PATIENTS: Sixty seven elderly patients (79.3 +/- 6.7 years) and 54 younger patients (40.8 +/- 9 years) were included in the study. RESULTS: Neither mean duration of evolution nor mean thyroid-stimulating hormone (TSH) level were different between the 2 groups. Two signs were found in more than 50% of the elderly patients (fatigue and weakness). Four signs were significantly less frequent in elderly patients (chilliness, paresthesiae, weight gain, and cramps). Mean number of clinical signs in the elderly (6.6 +/- 4) was significantly smaller than in young patients (9.3 +/- 4.7) (P < 0.01). CONCLUSIONS: Our results suggest that the presentation of hypothyroidism is altered in the elderly in comparison with young patients in that there are (1) fewer signs or symptoms and (2) diminished frequency of some classical signs. Our results underline the importance of TSH measurement in the elderly.

Effects of a slow-release formulation of the new somatostatin analogue lanreotide in TSH-secreting pituitary adenomas.

OBJECTIVE: Somatostatin analogues have been proposed for the treatment of thyrotrophinomas. However, this treatment requires several s.c. injections a day to be effective. The present study had the following aims: (i) appraisal of the efficacy of a single dose of two somatostatin analogues (lanreotide and octreotide) to acutely inhibit TSH secretion of TSH-secreting pituitary adenomas; (ii) assessment of the efficacy of a single injection of a slow release formulation of lanreotide (SR-L) in reducing TSH and thyroid hormone secretions in the same cases; and (iii) evaluation of the effects of SR-L used for 3-6 months on hormone secretion and tumour size. PATIENTS: Four patients with hyperthyroidism linked to a TSH-secreting pituitary adenoma found on pituitary magnetic resonance imaging (MRI) and subsequently proved by immunohistochemistry were studied. METHODS: In the first step of the study the patients received in a random order, vehicle, 150 micrograms octreotide and 500 micrograms lanreotide as a single s.c. injection. Measurements of plasma TSH, free T4 (fT4), free T3 (fT3) and free alpha subunit (fAS) levels were carried out before injection and then every other hour for 8 hours. In the second part of the study, after a basal blood sample (0800 h), each patient received 30 mg lanreotide as an i.m. injection of SR-L. Blood was sampled 2 hours later and then three times a week for 3 weeks in order to measure plasma TSH, fT4, fT3 and lanreotide levels using radioimmunoassays. The patients then received one SR-L injection twice or in one case three times a month for 3-6 months. Plasma TSH, fT4 and fT3 levels were measured monthly and a pituitary MRI was performed at the end of the treatment with SR-L. RESULTS: 500 micrograms lanreotide acutely reduced plasma TSH and fAS levels to the same extent as 150 micrograms octreotide. Two hours after a single i.m. injection of SR-L plasma lanreotide levels reached 7.8 +/- 0.6 micrograms/l and then progressively decreased, being 1.8 +/- 0.2 microgram/l on day 2 and 1.1 +/- 0.3 microgram/l on day 14 after the injection. Plasma TSH level decreased from basal value (mean +/- SEM 4.4 +/- 1.2 mlU/l) within 2 hours (2.5 +/- 0.8 mlU/l) and further declined to 0.8 +/- 0.2 ml/Ul on day 2 following the injection. Depending on the patient, plasma TSH levels were reduced for a period of 6-15 days. Plasma fT4, fT3 levels were normalized on day 2 and remained in the normal range for a period of time of 9-20 days. During long-term treatment, abdominal cramps and diarrhoea appeared, leading to interruption of the treatment in one patient. The treatment was well tolerated in the other three patients. Plasma TSH and thyroid hormone levels progressively decreased during the treatment. No change in adenoma volume was observed after 3-6 months of therapy. CONCLUSIONS: This study shows that (i) lanreotide is able to inhibit acutely TSH secretion in thyrotrophinomas and that a single s.c. injection of 500 micrograms lanreotide is as effective as 150 micrograms octreotide; (ii) SR-L appears to be able to reduce plasma TSH and to normalize fT4 and fT3 levels for 9-20 days in patients with thyrotrophinomas; (iii) this effect is maintained throughout the treatment using two or three SR-L injections monthly for months. These results suggest that SR-L could be used as a treatment of thyrotrophinomas and avoids the drawbacks of the modes of administration of other somatostatin analogues used in such cases.

[Major hypercalcemia revealing sarcoidosis]. / Hypercalcémie majeure révélatrice d'une sarcoïdose.

We reported a new case of sarcoidosis disclosed by a symptomatic severe hypercalcemia. Increase of 1,25-dihydroxyvitamin D is secondary to an extrarenal production by alveolar macrophages and sarcoid granuloma. Glucocorticoid administration produces a prompt and persistent decrease in serum and urinary levels of calcium.

[Education of a hospitalized diabetic population]. / Education d'une population diabétique hospitalisée.

During the second semester of 1981, all the diabetic patients who were hospitalized in the department (142 IDD and 75 NIDD) followed an educational program. Approximately half the patients were unable to follow the entire course, owing to visual, motor, intellectual or linguistic impairment. Few patients refused the course (8 cases). Evaluation of the theoretical knowledge at discharge showed poor results in 47% of IDD and 64% of NIDD, with patients in the latter group appearing to be less motivated. Advanced age, unemployment and alcoholism are detrimental factors. In contrast, among 71 IDD who followed only part of the course because of a handicap, 25 nevertheless acquired satisfactory knowledge, justifying an educational program with limited objectives. At follow-up at the outpatient clinic, insulin dependent patients exhibited better metabolic control, self-monitoring and acceptance of their disease; however, the patients who are seen at follow-up examinations are those who have the best theoretical knowledge. A comparative study of hospitalizations shows that admissions for hypoglycemia have decreased between 1978 and 1981, but education is not the only factor. The shortcomings and possible improvements are discussed.

[Haemodynamic and metabolic effects of exercise test in diabetic patients with arteritis treated or not with nicergoline (author's transl)]. / Effets hémodynamiques et métaboliques de l'épreuve d'effort chez l'artéritique diabétique traité ou non par la nicergoline.

A randomised crossover study in eleven diabetic patients with arteritis compared the effects of nicergoline (2,5 mg i.v.) or placebo on haemodynamic and metabolic parameters after exercise tests. Haemodynamic modifications after effort following placebo administration were typical: raised systolic blood pressure, and increased heart rate and myocardial oxygen requirements (systolic BP x heart rate). Modifications after similar effort following nicergoline involved an increase in systolic B.P. only, heart rate and myocardial oxygen requirements remaining unchanged. Blood lactic acid levels after effort and treatment were significantly higher (p. less than 0.01) than after effort without treatment. Overall metabolic and haemodynamic results demonstrate an increase in effort tolerance in diabetic patients with arteritis after nicergoline, this having been previously observed in healthy subjects.

[Multiple admission to hospital of diabetic patients (author's transl)]. / Les diabétiques multihospitalisés.

Within an 8 years' period, 29 insulin-dependent diabetic patients were admitted to hospital on more than 5 occasions, which represents 177 admissions for a total of 3407 days. In almost 70% of the cases loss of control of diabetes was the only reason for admission, and in 33% there was no urgency. Diabetes was unquestionably severe in all patients and truly unstable in 6, but socio-economic reasons accounted for at least one admission in 17 patients and for all admissions in 8. The remaining 64 admissions for uncontrolled diabetes were mostly due to the patients' carelessness. Twelve patients totalling 97 admissions never attended the out-patient clinic. Such carelessness seems to have arisen partly from reactive depression and partly from personality disorders, but the physicians's responsibility cannot be dismissed. In order to reduce the number of unnecessary admissions, diabetologists should provide improved patients' training, pay more attention to their psycho-affective problems and demand regular out-patient attendance.