Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients.

OBJECTIVE: Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the calcium-sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1. DESIGN AND PATIENTS: This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012. RESULTS: Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1], and the median 24-hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established. CONCLUSION: This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.

Medical therapy in patients with endogenous hypoglycaemia: Is euglycaemia achievable?

CONTEXT: While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalize plasma glucose levels can be useful. OBJECTIVE: The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions. PATIENTS AND METHODS: All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording. RESULTS: Twenty-seven patients (inappropriate insulin secretion n = 25 and IGF2 secretion n = 2), treated with diazoxide (n = 16), somatostatin analogues (n = 7), glucocorticoids (n = 3) or a combination of these treatments (n = 1) were enroled. Twenty-five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in seven patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in five patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%). CONCLUSION: Despite the disappearance of hypoglycaemia-related clinical symptoms and normalization of blood glucose self-monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo- and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo- or hyperglycaemic excursions.

Gestational diabetes and acromegaly: Single-centre experience of 14 pregnancies.

INTRODUCTION: The prevalence of gestational diabetes (GD) in women with acromegaly is rarely reported. The aims of this study were to evaluate the prevalence of GD in acromegalic women submitted to a systematic screening for GD and then to compare women with or without GD. PATIENTS AND METHODS: We studied 14 pregnancies in 11 women (34.0 ± 3.6 years) treated with somatostatin analogues after a pituitary surgery (n = 6) or as primary (n = 5) therapy, and treatment was discontinued at the time of pregnancy diagnosis for 13 pregnancies. One woman was diagnosed with acromegaly during pregnancy and was treated with octreotide LAR between 12 and 18 weeks of gestation. Before pregnancy, no women had diabetes mellitus, and GH/IGF-1 hypersecretion was uncontrolled in 6 women. RESULTS: Gestational diabetes was diagnosed during 7 pregnancies (50%) in 6 women (one woman had GD during her 2 pregnancies), according to fasting blood glucose (n = 5) or to an oral glucose tolerance test (n = 2). Before pregnancy, IGF-1 was not controlled in 4 GD+ and in 2 GD- women. Women with GD were not significantly older and had increased pregestational BMI (P = .02), with a more frequent family history of type 2 diabetes, no personal history of GD but of macrosomia for one patient. CONCLUSION: The prevalence of GD in our women is higher than that reported in the literature, probably resulting from the systematic GD screening and to the age of women. Therefore, routine screening of GD should be considered in women with acromegaly, particularly in those with risk factors for GD and with uncontrolled IGF-1 levels before pregnancy.

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies.

CONTEXT: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign. SETTING: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman. PATIENT: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1 mg dexamethasone suppression test. CT scan of the abdomen revealed a 35 mm left adrenal mass. INTERVENTION: The patient underwent a left adrenalectomy, and the histological study showed a 3 cm oncocytic adrenocortical carcinoma with signs of malignancy. RESULTS: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3ßHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery. CONCLUSION: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.

Decreased IGF-1 concentration during the first trimester of pregnancy in women with normal somatotroph function.

INTRODUCTION: A decrease of insulin-like growth factor-I levels (IGF-I) has been reported during the first trimester of pregnancy in women with acromegaly before the secretion of placental growth hormone (GH) progressively increases IGF-1 concentration. STUDY DESIGN: To evaluate variations of concentrations of IGF-1, insulin-like growth factor (IGF)-binding protein-3 (IGF-BP3) and GH during the first trimester of pregnancy in women with normal somatotroph function. PATIENTS AND METHODS: Sixteen women (median age 31 years) with as who were followed for benign thyroid disorders (n = 15) or prolactin-secreting microadenoma (n = 1) were evaluated before and in the first trimester of pregnancy. Serum concentrations of GH, IGF-1, IGF-BP3, TSH and estradiol (E2) were measured before and in the first trimester (5.4 ± 2.2 weeks of gestation). RESULTS: Before pregnancy, somatotroph and thyroid functions (median TSH 1.2 mU/L) were normal in all women. At the first trimester IGF-1 levels decreased significantly (before = 210 ng/mL, first trimester = 145 ng/mL, p < 0.001) with no significant change in GH (before = 1.5 ng/mL, first trimester = 0.84 ng/mL) or IGF-BP3 levels (before = 2.3 ng/mL, first trimester = 2.2 ng/mL), while estradiol levels increased significantly (before = 46.5 pg/100 mL, first trimester = 448.5 pg/100 mL, p < 0.001). CONCLUSION: In women with normal somatotroph function, IGF-1 levels decrease in the first trimester of pregnancy without changes in GH or IGF-BP3 levels. These results confirm liver resistance to GH as a consequence of the physiological increase of estrogens during the first trimester.

Glucose status in patients with acromegaly receiving primary treatment with the somatostatin analog lanreotide.

To describe glucose status changes in patients with acromegaly receiving somatostatin analog lanreotide as primary treatment. This retrospective, single-center study conducted during 1996-2008, included acromegalic patients receiving primary lanreotide treatment. Baseline and last follow-up visit assessments included glucose status (according to American Diabetes Association criteria), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) levels. Glucose control was considered improved when fasting plasma glucose or antidiabetic treatments were reduced, and deteriorated if fasting glucose was the same/higher but with increased antidiabetic treatments. 42 patients (median age 50 years; range 29-75 years) were included. At baseline, 26 (62%) were normoglycemic, eight (19%) had impaired glucose tolerance/fasting glycemia, and eight (19%) had diabetes mellitus; family history of diabetes mellitus was significantly associated with abnormal glucose status. At final visit, the mean (SE) lanreotide dose was 108 (21) mg/month. Median treatment duration was 23 months, range 3-138 months, and 74% of patients received the 120-mg dose. Median GH levels decreased significantly (baseline, 12 [5-20] µg/l; final visit, 2.1 [1.0-4.7] µg/l; P < 0.0001); IGF-1 levels were age- and sex-normalized in 33% of patients. Glucose control deteriorated in seven patients (17%) and improved from abnormal levels in 10 (24%). Deterioration was associated with smaller GH decreases (median change, -3.4 µg/l vs. -10.7 µg/l, P = 0.014) and improvement with trend to lower BMI and younger age. During primary lanreotide treated acromegalic patients 60% had no change, 24% had an improvement and 17% had a worsening of glucose status. Deterioration was significantly associated with smaller GH decreases during primary lanreotide treatment.

Tamoxifen enhances the control of acromegaly treated with somatostatin analog lanreotide.

We present the case of a 51-year old female patient with acromegaly that was resistant to somatostatin analogs and dopamine agonists. The patient was diagnosed with breast cancer requiring treatment with the anti-estrogen tamoxifen. Prior to initiating the treatment with tamoxifen, the IGF-I level was very high at 415% of the upper limit of normal for the patient's age and sex. During the tamoxifen treatment, the level of IGF-I dropped spectacularly down to normal levels. This observation highlights the effect of an anti-estrogen treatment in certain female patients with acromegaly.

Virilising ovarian tumour: a case associating a Sertoli-Leydig cell tumour and a Brenner tumour.

Ovarian Sertoli-Leydig cell tumours (SLCT), also termed arrhenoblastomas, are the most frequent virilising tumours in women of reproductive age. Very rare secretory Brenner tumours (BT) have been described, generally after the menopause. A 31-year-old woman sought medical advice for secondary amenorrhoea, progressive hirsutism and a 5-year history of virilisation syndrome with clitoromegaly. Testosterone was markedly high (285 ng/dl, N<85) with moderate elevation of delta 4-androstenedione (D4AD) (311 ng/dl, N <270), dehydroepiandrosterone sulfate (DHEAS) (366 µg/dl, N <340) and 17-hydroxyprogesterone (17OHP) (275 ng/dl). LH was 9 IU/l, FSH 4.3 IU/l, estradiol 60 pg/ml and progesterone 314 ng/100 ml. Cortisol was decreased (1.3 µg/dl) after the dexamethasone suppression test. Pelvic MRI showed a 5-cm right ovarian tumour with a 2.5 cm nodular component and cystic areas, and two nodules measuring 11 mm and 15 mm above the right and left ovaries. After right ovariectomy by laparoscopy, pathological examination concluded on a 3-cm SLCT and a 2-cm BT; the nodules above the ovaries were dysembryoplastic cysts. Postoperatively, testosterone level was normal after 24 h (26 ng/dl), estradiol and progesterone rapidly decreased, cyclic secretion then resumed and the patient menstruated at day 27. To our knowledge, this is the first report of an ovarian tumour associating a Sertoli-Leydig cell tumour and a Brenner tumour in a patient with virilisation syndrome which resolved after ovariectomy.

First-generation somatostatin receptor ligands and pregnancy: lesson from women with acromegaly.

INTRODUCTION: Few data are available on the risks of first-generation somatostatin receptor ligands (SRLs) during pregnancy in women treated for acromegaly. Current recommendations suggest the withdrawal of treatment at diagnosis of pregnancy. The aims of this literature review were to evaluate the teratogenic effects and the potential impact of SRLs on maternal and fetal outcomes by comparing acromegalic patients treated or not during pregnancy. PATIENTS AND METHODS: This study concerns 141 pregnancies in 127 women with acromegaly: 67 pregnancies in 62 women treated with SRLs during pregnancy and 74 pregnancies in 65 women not medically treated during pregnancy. A second analysis was then realized comparing women treated during 1st trimester only (36 pregnancies) and women treated longer (20 pregnancies). RESULTS: One malformation (ureteral stenosis) was reported in a newborn of a woman treated with SRL during pregnancy. No difference was found concerning maternal outcomes (gestational diabetes, hypertension, headaches, and delivery mode) and fetal outcomes (birth term, height, and weight). These results were also confirmed for the second analysis. CONCLUSIONS: This review of the literature did report one malformation without being able to prove a specific link with the first-generation SRL treatment. No significant impact on maternal and fetal outcomes is related to first-generation SRL treatment in women with acromegaly. The number of pregnancies is still low and more data are necessary to conclude on the total safety of this treatment during gestation. In the meantime, based on the nonthreatening data from this review of literature, SRL treatment can be continued and/or reintroduced during pregnancy if necessary (mainly for persistent headaches) in women with acromegaly.

Primary sellar melanocytic tumor: report of new case and literature review.

CONTEXT: Primary sellar melanocytic tumors are extremely rare, and they can mimic hormonally inactive pituitary macroadenoma both clinically and radiologically. OBJECTIVES: The aim of this study was to describe a new case of primary sellar melanocytic tumor, and place it in the context of published literature. DESIGN: This is a case report. PATIENT: The case of a 61-year-old woman presenting with a 2-month history of fatigue and progressive bitemporal hemianopia is described. Endocrine investigation revealed anterior pituitary insufficiency and hyperprolactinemia without diabetes insipidus. Magnetic resonance imaging demonstrated a sellar tumor mass with suprasellar extension compressing the optic chiasm, and intense gadolinium enhancement. Transsphenoidal surgical excision of the pituitary tumor was undertaken. Histological examination showed a melanocytic tumor. An extensive search failed to find evidence of any other primary or secondary site. Due to the presence of significant tumor residue at 3-month follow-up, another surgical resection was done followed by post-operative stereotactic radiotherapy of the sellar region. CONCLUSION: Primary sellar melanocytic tumors are exceptional lesions presenting most often as a tumor syndrome and/or anterior pituitary insufficiency mimicking a non-secreting pituitary macroadenoma. The management of these tumors consists of surgical removal of the tumor. However, surgery is often incomplete and stereotactic fractionated radiotherapy is frequently indicated.

Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature.

Cushing's syndrome due to AdrenoCorticoTropic Hormone (ACTH)-secreting pheochromocytoma has been rarely reported during pregnancy and post-partum. We report the case of a 30-year-old woman who presented 3 months after delivery acute psychiatric signs and rapid progressive features of Cushing's syndrome. Hormonal tests confirmed ACTH-dependant Cushing's syndrome. A computed tomography scan revealed a 25 x 30 mm tumoral mass in the left adrenal gland and octreoscan scintigraphy showed only an uptake of the radiolabelled octreotide by the adrenal tumor. Fractionated 24-h urinary catecholamines and metanephrines were in the normal range, except for slightly increased adrenalin levels. A left laparoscopic adrenalectomy was performed with acute pulmonary oedema following the anesthesia. Histological examination revealed a 3.5 x 2.5 cm adrenal tumor consistent with a pheochromocytoma without signs of malignancy. The tumor cells immunostained for ACTH and diffuse hyperplasia of adrenocortical cells was observed. After surgery and short stay in intensive care unit, clinical and biological signs rapidly improved and both anti-hypertensive treatment and insulin injections were withdrawn. Genetic testing did not reveal germline mutations in RET protooncogene, Von Hippel Lindau and succinate deshydrogenase genes.

Weight-loss with activation of brown fat: Suspect pheochromocytoma.

INTRODUCTION: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma. CASE STUDY: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. 18FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery. CONCLUSION: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.

Significant prevalence of NR3C1 mutations in incidentally discovered bilateral adrenal hyperplasia: results of the French MUTA-GR Study.

BACKGROUND: Recently discovered mutations of NR3C1 gene, encoding for the GR, in patients with glucocorticoid resistance and bilateral adrenal incidentalomas prompted us to investigate whether GR mutations might be associated with adrenal hyperplasia. OBJECTIVE: The multicenter French Clinical Research Program (Muta-GR) was set up to determine the prevalence of GR mutations and polymorphisms in patients harboring bilateral adrenal incidentalomas associated with hypertension and/or biological hypercortisolism without clinical Cushing's signs. RESULTS: One hundred patients were included in whom NR3C1 sequencing revealed five original heterozygous GR mutations that impaired GR signaling in vitro. Mutated patients presented with mild glucocorticoid resistance defined as elevated urinary free cortisol (1.7 ± 0.7 vs 0.9 ± 0.8 upper limit of normal range, P = 0.006), incomplete 1 mg dexamethasone suppression test without suppressed 8-AM adrenocorticotrophin levels (30.9 ± 31.2 vs 16.2 ± 17.5 pg/mL) compared to the non-mutated patients. Potassium and aldosterone levels were lower in mutated patients (3.6 ± 0.2 vs 4.1 ± 0.5 mmol/L, P = 0.01, and 17.3 ± 9.9 vs 98.6 ± 115.4 pg/mL, P = 0.0011, respectively) without elevated renin levels, consistent with pseudohypermineralocorticism. Ex vivo characterization of mutated patients' fibroblasts demonstrated GR haploinsufficiency as revealed by below-normal glucocorticoid induction of FKBP5 gene expression. There was no association between GR polymorphisms and adrenal hyperplasia in this cohort, except an over-representation of BclI polymorphism. CONCLUSION: The 5% prevalence of heterozygous NR3C1 mutations discovered in our series is higher than initially thought and encourages GR mutation screening in patients with adrenal incidentalomas to unambiguously differentiate from Cushing's states and to optimize personalized follow-up.

[Fertility before and after treatment of patients with Leydig cell tumour]. / Fertilité avant et après traitement des patients présentant une tumeur à cellule de Leydig.

OBJECTIVE: To determine the long-term fertility status of patients treated for Leydig cell testicular tumour. MATERIAL AND METHODS: [corrected] In a series of 506 testicular tumours observed in the Midi-Pyrenées region between 1980 and 1998, 17 were Leydig cell tumours (3.3%) and constituted the study population. Andrological records were available for all patients. Information concerning fertility before and after orchidectomy was obtained by validated letter questionnaire. All patients completed the questionnaire. RESULTS: The mean follow-up was 84 months (range: 36-173). The mean age at diagnosis was 32 years (range: 24-51). The presenting symptom was gynaecomastia in 9 cases (53%), enlarged testis in 4 cases (24%), scrotal pain in 2 cases (12%) and male infertility in 2 cases (12%). Before onset of their disease, 13/17 (76.5%) patients had tried to have a child and 6 (46.2%) had successfully fathered a child. After treatment of their Leydig cell tumour, 10/17 (58.8%) had tried to have a child and 7 (70%) were successful. CONCLUSION: The population of men with Leydig cell tumour of the testis is a population with decreased fertility before treatment of the tumour. Resection of the tumour improves this situation, but 3 out of 10 patients remain infertile, indicating the need for semen storage measures in this population.

[Non-deferential male contraception: review of the literature]. / Contraceptions masculines non déférentielles: revue de la littérature.

OBJECTIVES: To review the state of progress of the various male contraceptive methods (with the exception of deferential methods). MATERIAL AND METHODS: A review of the literature was performed by using the key words: male/contraception, limiting the search to original articles in English and French. Articles on vasectomy and the other deferential methods of contraception are not considered in the present review. RESULTS: Three methods of male contraception are widely used at the present time: withdrawal, male condom and vasectomy, although other types of male contraception have been shown to be effective, including hormonal contraception, which appears to be the most promising technique and the subject of the majority of research. Other contraceptive methods (immunological, thermal...) could constitute possible alternatives. CONCLUSION: Male contraception remains under-used, as only male condoms are commonly used (apart from withdrawal and vasectomy). Consequently, new research protocols in the field of male contraception must be strongly encouraged.

[Retroperitoneal laparoscopic surgery for phaeochromocytoma: analysis of morbidity and haemodynamic instability]. / Chirurgie du phéochromocytome par laparoscopie rétropéritonéale: analyse de la morbidité et de l'instabilité hémodynamique.

OBJECTIVE: To study the morbidity and haemodynamic parameters on a consecutive series of adrenalectomies performed Jbr phaeochromocytoma by retroperitoneal laparoscopy. MATERIAL AND METHODS: The study population comprised 23 phaeochromocytomas in 20 patients treated by controlled retroperitoneal laparoscopic surgery. The following parameters were studied: intraoperatively: operating time, blood loss, blood pressure, heart rate, and postoperatively: infectious, haemorrhagic and thromboembolic complications. RESULTS: The mean operating time was 156 minutes (range: 105-224). Mean blood loss was 58 ml (range: 0-300). Intraoperatively, 1500 of patients presented a peak SBP >220 mmHg and 70% presented a peak SBP >200 mmHg. In contrast, 200 of patients presented a nadir SBP <60 mmHg, but no patient presented a nadir SBP less than 40 mmHg. One case of intraoperative haemorrhage was observed (4.3%). Three postoperative complications (1 case of respiratory distress, 1 case of haemorrhagic shock, and 1 abscess) were observed (13%). CONCLUSION: Laparoscopic surgery for phaeochromocytoma is associated with a risk of haemodynamic instability. Phaeochromocytoma surgery should therejbre continue to be performed in specialized centres (surgical, anaesthetic and endocrinological).

[Hypoglycemia in nondiabetic patients: When is the 72-hour-fast test required and how can it be interpreted?]. / Hypoglycémies chez le sujet non diabétique : quand faut-il réaliser une épreuve de jeûne et comment l'interpréter ?

Whereas hypoglycaemia is uncommon in nondiabetic patients, it is a frequent reason for consultation. Hypoglycaemia is confirmed when criteria of Whipple's triad are fulfilled. If a venous sample cannot be collected when hypoglycemia occurs spontaneously, a 72-hour-fast test should be performed firstly to affirm the reality of hypoglycaemia and secondly to make the etiological diagnosis. Before carrying out this long and expensive test, the obvious causes of hypoglycaemia must be ruled out: iatrogenic, severe prolonged undernutrition, liver or renal deficiency, adrenal insufficiency, IGFII or pro-IGFII secreting tumours…At the time of hypoglycemia, plasma insulin≥3mUI/L, C-peptide≥0.6ng/mL, proinsulin≥5pmol/L associated with plasma beta-hydroxybutyrate≤2700µmol/L provide evidence for inappropriate insulin secretion. The lack of hypoglycaemia after a 72-hour-fast test rules out, in the majority of cases, organic hypoglycaemia.

Local recurrence of pheochromocytoma in multiple endocrine neoplasia type 2A: a diagnostic and therapeutic challenge.

In a patient with multiple endocrine neoplasia type 2A (MEN2A), an inverted physiological ratio between urinary normetanephrines and metanephrines is an early marker of recurrence in epinephrine-secreting pheochromocytoma, and 131I MIBG treatment appears to be a useful therapeutic option in order to avoid multiple invasive surgical procedures in pheochromocytomatosis.

Octreotide in insulinoma patients: efficacy on hypoglycemia, relationships with Octreoscan scintigraphy and immunostaining with anti-sst2A and anti-sst5 antibodies.

OBJECTIVE: We studied the efficacy of octreotide treatment on hypoglycaemia in patients with insulinoma and its relationships with Octreoscan scintigraphy and the presence of tumoral somatostatin receptors sst2A and sst5. DESIGN AND METHODS: 17 patients with insulinoma were evaluated using (i) evaluation of blood glucose, insulin and C-peptide during a short 100 mug octreotide test in fasting patients and/or treatment over 8 days-8 months with octreotide, (ii) Octreoscan scintigraphy and (iii) immunostaining of the tumor with anti-sst2A and anti-sst5. RESULTS: Octreotide was effective on hypoglycaemia in 10/17 patients. Octreoscan scintigraphy detected 4/17 insulinomas. sst2A receptor was detected in 7/17 insulinomas and sst5 in 15/17 insulinomas. Octreotide was effective on hypoglycaemia in those seven patients with sst2A receptor-expressing insulinoma, and in three patients with undetectable sst2A receptor and detectable sst5; it was ineffective in six patients whose tumor expressed the sst5 receptor with undetectable sst2A and in one patient with undetectable sst2A and sst5 receptor. CONCLUSIONS: Octreotide is an effective treatment of hypoglycaemia in more than 50% of patients with insulinoma. Detection of responsive patients was better based on a positive short test with subcutaneous octreotide than on the results of Octreoscan scintigraphy. Positive anti-sst2 receptor immunostaining is associated with efficacy of octreotide treatment, but does not account for all cases of responsiveness to octreotide. Expression of sst5 receptor does not appear to explain per se the efficacy of octreotide on sst2A-negative insulinomas.

Primary Medical Treatment of Thyrotropin-Secreting Pituitary Adenomas by First-Generation Somatostatin Analogs: A Case Study of Seven Patients.

BACKGROUND: The first-choice treatment of thyrotropin (TSH)-secreting pituitary adenomas is surgical adenomectomy, with 40-60% of patients cured after surgery. The presence of somatostatin receptors on the adenomatous cells suggests that first-generation somatostatin analogs (octreotide, lanreotide) could be used as an adjuvant treatment to surgery for TSH-secreting pituitary adenomas. The aim of this study is to describe the efficacy and safety of primary medical treatment with first-generation somatostatin analogs in patients with a TSH-secreting pituitary adenoma. METHODS: Retrospective study on 7 patients (5 women, 2 men) aged 57±14 years with pure TSH (n=4) or mixed TSH/GH (n=3) secreting pituitary adenomas primarily treated with first generation somatostatin analogs. Magnetic resonance imaging revealed a microadenoma in 3 patients and a macroadenoma in 4 patients. The follow-up period was 8.5±7.3 years. RESULTS: At initial diagnosis, the patients presented with thyrotoxicosis with elevated free thyroxine (26.5±6.5 pg/mL) and free triiodothyronine (7.3±0.9 pg/mL) levels and a mean TSH of 4.3±1.4 mU/L. During somatostatin analog treatment, free thyroid hormones and TSH levels normalized after 4.4±3.9 and 7.0±8.4 months, respectively. At the time of the last visit, 6 patients were biochemically controlled. Adenoma volume decreased in 6 patients and a decrease in adenoma volume persisted in 2 patients several years after initiation of somatostatin analog treatment. Safety of treatment was good and no patients discontinued somatostatin analogs due to side effects. CONCLUSION: This study confirms the efficacy of primary medical treatment with first-generation somatostatin analogs in terms of hormonal control and tumor volume reduction in patients with TSH-secreting pituitary adenomas, and its good safety profile. First-generation somatostatin analogs may serve as a medical alternative to surgical treatment, especially in patients where surgery is contraindicated or in subjects presenting with invasive macroadenomas that render complete surgical resection difficult.