Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test.

BACKGROUND: Adult growth hormone (GH) deficiency must be diagnosed before prescribing therapeutic recombinant human GH. We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency (GHD) using IGF-1 determination as a first step. METHODS: In 2000 and 2001, we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test (ITT), the reference test for the diagnosis of GHD, with concomitant Insulin-like growth factor-1 (IGF-1) determination, a marker of somatotropic function. Patients were classified as GHD (peak GH concentration<3 ng/ml with the ITT) or normal. SETTING: Monocenter prospective study in a tertiary referral center. RESULTS: GHD was diagnosed in 61 subjects. Using a ROC curve, a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5%. A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients, avoided 46/142 ITT and reduced the cost of diagnosis by 15%. CONCLUSION: We propose the use of a strategy consisting of IGF-1 determination followed, if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults.

Increased calcitonin level in thyroid nodules without medullary carcinoma.

BACKGROUND: Basal calcitonin measurement is routinely performed in patients with a thyroid nodule to detect medullary carcinoma. However, increased calcitonin does not always correlate with medullary carcinoma. The aim of this study was to analyse increased calcitonin levels in patients without medullary carcinoma and to find out whether absence of this carcinoma can be predicted with certainty. METHODS: From 1992 to 2003, 5018 patients with thyroid nodules underwent thyroid surgery. A retrospective analysis of preoperative increased calcitonin levels in 67 of these patients was performed. RESULTS: Pathology revealed medullary carcinoma in 16 patients (group I), micromedullary carcinoma in 13 (group II) and no medullary carcinoma in 38 (group III). In group III, 30 patients had C-cell hyperplasia. The mean basal calcitonin level was 6250 pg/ml in group I (39-62 500), 109.6 pg/ml in group II (10-728) and 25.5 pg/ml in group III (10.5-145). The mean pentagastrin-stimulated calcitonin level was 1074.1 pg/ml in group II (26-5700) and 67.6 pg/ml in group III (10-205). CONCLUSION: There is an overlap of thyroid C-cell pathology for medullary carcinoma, micromedullary carcinoma and C-cell hyperplasia that occurs when basal calcitonin is between 10 and 145 pg/ml and pentagastrin-stimulated calcitonin between 10 and 205 pg/ml. In these patients, since medullary carcinoma cannot be completely excluded, total thyroidectomy should be recommended.

Advances in diagnostic practices affect thyroid cancer incidence in France.

OBJECTIVE: To analyse trends in diagnostic practices of thyroid diseases and to relate them to the increase in thyroid cancer incidence in France over time. DESIGN: From 1980 to 2000, a French retrospective multicentric (three endocrinology and three nuclear medicine centres) study of thyroid diseases was conducted on 20 consecutive unselected patients' records, sampled every 5 years in each centre. METHODS: Characteristics of the population and diagnosis procedures (thyroid ultrasonography (US), radionuclide scan, cytology and hormonal measurements) were described over time. Changing trends in operated patients and in cancer prevalence were analysed as well as the impact of practices on cancer incidence. RESULTS: The study included 471 patients (82% female, mean age 46.7, range 9-84 years), referred for nodular thyroid diseases (66.7%) or thyroid dysfunctions (33.3%). A significant increase in US (3 to 84.8%) and cytological practices (4.5 to 23%), and a decrease (89.4 to 49.6%) in radionuclide scan procedures were observed over time. Although the proportion of patients undergoing surgery remained constant (24.8%), the prevalence of cancer increased among operated patients from 12.5 to 37% (P=0.006). In a Cox's proportional hazard model stratified on the clinical characteristics of patients, only the cytological practice, regardless of its results, was significantly associated with the occurrence of cancer: relative risk (RR)=4.4 (95% confidence interval (CI): 1.1-16; P=0.04). CONCLUSIONS: From 1980 to 2000, a major evolution in clinical practices has led to the increase in thyroid cancer reported in France. Such changes in medical, as well as in surgical and pathological, practices must be taken into account in incidence measurement.

[Pituitary germinoma presenting as a pseudotumoral lymphocytic hypophysitis in a man]. / Germinome hypophysaire révélé par une hypophysite lymphocytaire pseudo-tumorale chez un homme.

A 45-year-old man presented with headaches and extraocular muscle palsy due to a sellar mass extending into the right cavernous sinus. Hormonal determinations revealed a gonadotrophic insufficiency. A transsphenoidal surgical removal revealed a lymphocytic hypophysitis with fibrosis and necrosis. Rapid growth of the pseudotumor was noted despite a high dose steroid therapy (1 mg/kg/d) for a month. Further biological and histopathological investigations were performed. They showed a high cerebrospinal fluid (CSF) B-human chorionic gonadotropin (ss-HCG) level of 12 UI/L (normal<5 UI/L), normal plasma BHCG level, and undetectable CSF and plasma alpha-fetoprotein levels. The tumors cells showed a positive reactivity for placental alkaline phosphatase and for vimentin. These findings were consistent with an inflammatory lymphocytic process caused by an intrasellar germinoma. Chemotherapy was ill-tolerated and external radiotherapy was ineffective.

[Primary thyroid lymphoma: report of 8 cases]. / Lymphome malin primitif de la thyroïde: à propos de huit cas.

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up. RESULTS: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up. CONCLUSION: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

Efficacy of the long-acting octreotide formulation (octreotide-LAR) in patients with thyrotropin-secreting pituitary adenomas.

The presence of somatostatin receptors on TSH-secreting pituitary adenomas allows treatment of central hyperthyroidism with somatostatin analogs. Six women and 5 men (mean +/- SEM age, 43 +/- 3 yr) presented TSH-secreting pituitary adenomas (micro, n = 2; macro, n = 9). Seven patients had previously been treated with partial surgical removal (n = 6) and/or external radiation (n = 4) of their adenoma at least 1 yr before the study, whereas 4 patients had not been treated before somatostatin analog therapy. TSH, free T(4), and free T(3) levels were in the normal range during treatment with sc injections (n = 9) or continuous infusion (n = 2) of octreotide (280 +/- 25 microg/day). Mean thyroid hormone levels increased (P < 0.01) after the washout period (34 +/- 6 days). The patients received monthly im injections of 20 mg Octreotide-LAR. In patients with an elevated free T(4) level after 3 months (n = 1) the Octreotide-LAR dose was increased to 30 mg. After 3 months of Octreotide-LAR treatment, TSH, free T(4)/T(3), and alpha-subunit levels decreased, and 10 patients were euthyroid with normal free T(4) levels. These results remained at the same level over the next 3 months. There were no statistically significant differences in the TSH and free T(4) responses to sc octreotide or im Octreotide-LAR between previously untreated patients and patients who had undergone surgical resection and/or pituitary radiation before somatostatin analog treatment. During Octreotide-LAR treatment, minor digestive problems or moderate discomfort at the injection site, lasting less than 48 h, were reported in 6 and 5 patients, respectively. Gallbladder echographies did not reveal new gallstones during Octreotide-LAR treatment. In conclusion, this study shows that monthly im Octreotide-LAR is as effective as daily sc octreotide in controlling hyperthyroidism in patients with TSH-secreting pituitary adenomas, in both previously untreated patients and patients treated with surgery and/or pituitary radiotherapy. Octreotide-LAR is well tolerated, except for minor digestive problems or mild pain at the injection site. Therefore, Octreotide-LAR appears to be a useful therapeutic tool to facilitate medical treatment of TSH-secreting pituitary adenomas in patients who need long-term somatostatin analog therapy.

Prediction of major coronary events by coronary risk profile and silent myocardial ischaemia: prospective follow-up study of primary prevention in 72 diabetic patients.

UNLABELLED: The aim of this study was to examine the predictive value of coronary risk profile (CRP) for major coronary events in patients screened for silent myocardial ischemia (SMI). We studied 72 diabetic patients, aged 41 to 65 years, recruited consecutively at the Poitiers diabetes clinic. All patients had at least one cardiovascular risk factor associated with diabetes mellitus (type 1 diabetes duration > or =15 years, dyslipidaemia, smoking, hypertension, micro/macro-albuminuria). A structured questionnaire, physical examination and resting electrocardiogram provided no evidence of coronary heart disease. SMI was defined as positive exercise electrocardiogram and/or dipyridamole thallium myocardial scintigraphy. CRP was estimated using the Framingham equation adapted to the French population. We defined a high CRP value as annual CRP > or =1.5%. Major coronary events (MCE) were defined as myocardial infarction, ischaemic heart failure, unstable angina or sudden death. Twenty-one patients with type 1, and 51 with type 2 diabetes were followed up for 39+/-12 months: 30 women and 42 men, aged 55+/-7 years with diabetes duration of 16 +/- 11 years (mean +/- SD). SMI was detected in 8 patients. Major coronary events occurred in 8 patients, 2 of whom had SMI. High CRP was found in 18 patients, 3 of whom had MCE. CRP was significantly higher in those patients with a major coronary event (1.71 +/- 1.11 versus 1.03 +/- 0.56%; p=0.048), but not in those with SMI (1.19 +/- 0.72 vs 1.09 +/- 0.67%; p=0.654). In Kaplan-Meier survival analysis, a high CRP was associated with the risk of a major coronary event (log-rank=5.36; p=0.021), whereas SMI was not (log-rank=2.02; p=0.155). The cumulative incidence of MCE in those patients with high and low CRP was 8.08 (0.49-15.67) vs 2.15 (0.06-4.22) events per 100 patient year of follow-up, respectively. CONCLUSION: CRP had a good predictive value for major coronary events regardless the presence of SMI. Prevention should therefore be focused primarily on patients with high CRP, wether or not they have SMI.

Multicentre study of thyroid nodules in patients with Graves' disease.

BACKGROUND: The association of Graves' disease with thyroid nodules and thyroid carcinoma is rarely reported. The incidence seems to be increasing according to recent literature. The aim of this multicentre study was to review patients who had surgery for Graves' disease associated with thyroid nodules, and to evaluate the risk of thyroid carcinoma. METHODS: A retrospective study was made of 557 consecutive patients who underwent operation for Graves' disease between 1991 and 1997 in five endocrine surgery departments. Each patient underwent clinical, biochemical, ultrasonographic and scintigraphic evaluation. None of the patients had had previous radioactive iodine therapy or external irradiation. Surgery consisted of either a subtotal or total thyroidectomy. RESULTS: Nodules were observed before operation in 140 patients (25.1 per cent). Thyroid carcinoma was diagnosed in 21 patients (15.0 per cent), always inside a nodule. The incidence of thyroid carcinoma associated with Graves' disease was 3.8 per cent (21 of 557 patients): 20 papillary and one follicular carcinoma. The carcinoma was multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A nodule was palpable in four patients. CONCLUSION: This multicentre study of patients having thyroidectomy for Graves' disease showed that 3.8 per cent had a carcinoma; the rate of carcinoma in cold nodules was 15.0 per cent. Surgery should be advised in any patient with Graves' disease and a thyroid nodule; the operation should be total thyroidectomy.

[Basedow's disease and thyroid nodules. A common association]. / Maladie de Basedow et nodules thyroïdiens. Une association non exceptionnelle.

The frequency of thyroid cancer associated with Graves' disease is a controversial subject. The authors retrospectively studied 110 consecutive patients operated for Graves' disease between 1991 and 1996. Each patient was evaluated by clinical and laboratory examination, ultrasound and isotope scan. None of the patients had a history of external beam cervical radiotherapy or radioactive iodine. All patients were treated by total or subtotal thyroidectomy. Thyroid nodules were detected in 28 patients (24 women, 4 men), and 6 of them corresponded to papillary carcinoma (5.5% of patients with Graves' disease and 21.4% of patients with Graves' disease associated with nodules). These data suggest the value of surgery in Graves' disease associated with thyroid nodules.

[Thyroid nodules associated with Graves' disease: another argument for surgical treatment]. / Nodules thyroïdiens associés: un argument de plus en faveur du traitement chirurgical de la maladie de Basedow.

Much controversy surrounds the incidence of thyroid cancer associated with Graves' disease. We studied retrospectively 110 patients operated on for Graves' disease between 1991 and 1996. Each patient was evaluated by clinical exam, biological test, ultrasonography, and scintigraphy. No patient had a history of prior external radiation to the head or the neck. All patients underwent near total or total thyroidectomy. Nodules in the thyroid were detected in 28 cases: 6 were papillary carcinoma (5.5% from patients with Graves' disease, and 21.4% from patients with Graves' disease associated with thyroid nodules). These data suggest interest of surgery in Graves' disease associated with thyroid nodules.

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

OBJECTIVE: Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study. DESIGN: Prospective study evaluating the prevalence of unilateral IMC uptake (tumour uptake with no visualization of the contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and the contralateral adrenal glands) in patients with unilateral incidentaloma. Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM) in the two scintigraphic groups thus defined. PATIENTS: Thirty-five patients with a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan. MEASUREMENTS: The IMC scan was performed in basal conditions (baseline scan) and after DXM (suppression scan). Adrenocortical function assessment included basal measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test. RESULTS: The baseline scan showed 16 patients (46%) with unilateral uptake (group A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an overnight DXM suppression test (P = 0.02), than did patients in group B. In addition, 3 patients in group A failed the overnight and the low-dose DXM suppression tests. Adrenal masses were larger in group A than group B (P = 0.04) and an inverse correlation was found in the whole population between tumour size and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14 patients (7 in each group), patients in group A continued to exhibit unilateral tumour uptake and bilateral uptake was suppressed in 72% of patients in group B. An adrenal mass was removed in 3 patients of group A with confirmed benign adrenocortical adenomas. In the post-surgical period, the contralateral gland was again visualized in a baseline scan and the hormonal evaluation returned to the normal range. CONCLUSION: Unilateral 131I-6 beta-iodomethylnorcholesterol tumour uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and scintigraphic profiles obtained after dexamethasone, as well as hormonoscintigraphic changes observed after surgery, provide evidence that unilateral uptake is related to functioning adenomas with various degrees of autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could be a valuable tool for screening 'subclinical' Cushing's adenomas.

Analysis and prevention of recurrent goiter.

The current study was done to analyze our experience with recurrent goiter. Prevention must be stressed because reoperations of the thyroid gland present technical difficulties and are associated with an increased risk of hypoparathyroidism and permanent hoarseness. Nodular recurrences occurred in 36 of 1,456 patients (2.5 percent) who underwent thyroidectomy between 1968 and 1983. All patients had the initial operation at Jean Bernard Hospital, Poitiers, France, and had follow-up evaluation from five to 20 years. Multinodular goiter accounted for 70 percent of the recurrences. Sixty percent of the recurrences were in patients with multinodular goiters. Recurrent goiter was usually first detected about eight years after thyroidectomy. Thirty patients with recurrence had reoperations. Two patients had paralysis of the vocal cord and one patient had permanent hypoparathyroidism. Recurrent goiter may occur because of the development of new nodules (true recurrence) or because of the growth of "residual" or persistent macroscopic or microscopic nodules left at the previous thyroid operation. Intraoperative digital palpation of the entire thyroid gland is essential for detecting residual macroscopic thyroid nodules, and all enlarged nodules should be removed. Thyroid-stimulating hormone (TSH) suppressive therapy is recommended by some authorities to prevent "true" recurrences, although its efficacy is debated. Since recurrence is uncommon in the current series, perhaps TSH suppressive therapy should only be used in high-risk patients. In the current experience, only the multinodular character of the nodules in euthyroid patients has a significant correlation with subsequent development of recurrent goiter (p < 0.01), and one must consider patients with multinodular goiter at risk for recurrence. Once TSH treatment is begun, it will logically be continued for life. Total thyroidectomy has been recommended by some endocrine surgeons for treating patients with multinodular goiter. We prefer subtotal thyroidectomy and reserve total thyroidectomy for patients when no normal thyroid tissue can be preserved because only 2.5 percent of the patients in the current study had recurrent goiter. Prevention of residual nodules is probably best assured by systematic palpation during operation of the two thyroid lobes. This considerably lessens the risk of recurrence. Since nodular recurrences occurred in only 2.5 percent of the patients in the current study, although multinodular goiter must be considered at risk for recurrence, we do not recommend systematic total thyroidectomy in multinodular goiter.

[Corticotropic macroadenoma: clinical, hormonal, radiological and immunocytochemical study of 6 cases]. / Le macroadénome corticotrope: étude clinique, hormonale, radiologique et immunocytochimique de 6 observations.

We report 6 cases of corticotroph macroadenomas which show heterogeneity of clinical and biological features (from Cushing's syndrome to silent adenoma) and heterogeneity of immunocytochemical staining. One patient reported on had skin hyperpigmentation and ACTH hypersecretion without clear abnormal adrenocortical function; we believe that this patient's plasma contained ACTH with very low bioactivity.

Bilateral symptomatic adrenal myelolipoma.

Adrenal myelolipomas are rare, nonfunctioning benign tumors that consist of mature fat and bone-marrow elements. In the first half of this century, most adrenal myelolipomas were found incidentally at autopsy. These tumors are usually unilateral and asymptomatic. Today they are detected by ultrasonography, computerized tomography, or magnetic resonance imaging scan, done for other reasons. Adrenal myelolipomas can be diagnosed because of their characteristic images. Thus they are classified as "incidentalomas." We report the case of a 50-year-old man who had bilateral adrenal myelolipomas and whose right-side tumor was symptomatic. To our knowledge it is the third operated case reported in the literature. A right adrenalectomy was performed, keeping the asymptomatic left adrenal myelolipoma to preserve adrenal function.

[Hyperthyroidism caused by metastatic choriocarcinoma. A new male case]. / Hyperthyroïdie par choriocarcinome métastasé. Une nouvelle observation masculine.

The authors report a case of hyperthyroidism induced by a metastatic choriocarcinoma (retroperitoneal, lungs, vertebral and epidural localisations) in a 49 year old man. Tachycardia and possibly weight loss were the only clinical signs of thyrotoxicosis. Chemotherapy led to a remission of hyperthyroidism and tumoral syndrome for 4 months. Neoplasia relapsed and circulating levels of thyroid hormones were increased during the final stages. This is the fifth male reported case of choriocarcinoma associated with hyperthyroidism. Many previous studies suggest that hyperthyroidism is induced by HCG thyroid stimulating activity.

[Reversible bone marrow hypoplasia in a case of male anorexia nervosa]. / Hypoplasie médullaire réversible au cours d'une anorexie mentale masculine.

The authors report the case of a 17 year old boy with anorexia nervosa and bone marrow hypoplasia. After a 14 kg weight loss, the patient had pancytopenia, morphological abnormalities of the red cells (acanthocytes, schizocytes), without hemolysis, and hypogonadotropic hypogonadism. Bone marrow biopsy showed a marked reduction of hematopoietic cells with striking diffuse interstitial oedema. Clinical recovery, during the next 6 months, was associated with a return of the haematological changes to normal and to a disappearance of hypogonadism. Anorexia nervosa is a rare entity in boys. In all probability, bone marrow hypoplasia is not a well known feature of this disorder. The haematological changes are reversible with improvement of nutritional status.