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.

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.

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.

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.

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.

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.

[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.

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.

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.

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.

Increased plasma ß-hydroxybutyrate levels during the fasting test in patients with endogenous hyperinsulinaemic hypoglycaemia.

OBJECTIVE: The objective of the present study was to determine whether a plasma ß-hydroxybutyrate (BOHB) level >2700 µmol/l during the 72-h fasting test is sufficient to rule out the diagnosis of endogenous hyperinsulinaemic hypoglycaemia (EHH). RESEARCH DESIGN AND METHODS: We retrospectively studied BOHB levels in 39 patients with EHH who had undergone a 72-H fasting test to make the diagnosis of EHH, and we compared EHH patients with BOHB levels 2700 MOL/L (group 1), EHH PATIENTS with BOHB levels 2700 MOL/L (group 2) and 59 controls (median glycaemia: 3.2  mmol/l and median BOHB: 6095 µmol/l). RESULTS: During a 72-h fasting test, nine patients (group 1) had BOHB levels >2700  µmol/l (median 6140 and range 2957-7824) and 30 patients (group 2) had BOHB levels <2700 µmol/l (median 542 and range 0-2607). In group 1, four patients had undergone partial pancreatectomy previously and were evaluated for the recurrence of hypoglycaemia, whereas none of the group 2 patients had been operated. The duration of the fasting test was longer in group 1 than in group 2 (P<0.0001), and at the end of the fasting test, plasma glucose concentrations were not significantly different (P=0.0617), but insulin (P=0.004), C-peptide (P=0.0015) and proinsulin (P=0.0038) levels were significantly lower in group 1 patients than in group 2 patients, suggesting lower insulin secretion and/or impaired glycaemic counter-regulation. CONCLUSION: During a fasting test, a BOHB level >2700 µmol/l is observed in some EHH patients, suggesting that BOHB levels cannot rule out the recurrence of EHH, in particular, after partial pancreatectomy.

Virilizing sclerosing-stromal tumor of the ovary in a young woman with McCune Albright syndrome: clinical, pathological, and immunohistochemical studies.

CONTEXT: McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait skin pigmentations, and gonadotropin-independent sexual precocious puberty, resulting from a somatic postzygotic activating mutation of the GNAS1 gene. SETTING: We report a virilizing sclerosing-stromal tumor of the ovary in a young female with MAS. PATIENT: She presented polyostotic fibrous dysplasia of the left upper and lower limbs and a café-au-lait skin spot in the posterior area of the neck. She had a history of precocious puberty, diagnosed at the age of 6 years and treated with cyproterone acetate until the age of 10 years; then she developed central puberty with severe oligomenorrhea. At the age of 23 years, she was hospitalized for a virilization syndrome including hirsutism, acne, deepening of the voice, amenorrhea, and clitoromegaly. Serum levels of T were dramatically increased (1293 ng/dl; normal range, 10-80). The abdominal computed tomography scan revealed a solid mass located on the left ovary. INTERVENTION: An ovariectomy was performed, and histological examination revealed a sclerosing-stromal tumor with pseudolobular pattern. RESULTS: Immunohistochemical studies revealed that the tumor cells expressed all steroidogenic enzymes involved in androgen synthesis. Molecular analysis revealed that ovarian tumor cells harbored the Arg 201 activating mutation in the GNAS1 gene. After surgery, T levels returned to normal, the patient retrieved a normal gonadal function, and she was able to become pregnant. CONCLUSION: This observation extends the clinical spectrum of ovarian pathology of women with MAS. However, the mechanisms causing this ovarian tumor remain unclear, even if the gsp oncogene has been implicated in the pathogenesis of some gonadal tumors.

Retroperitoneoscopic adrenalectomy: comparison of retrograde and antegrade approach among a series of 279 cases.

OBJECTIVE: To compare the results of retroperitoneal laparoscopic adrenalectomy using the antegrade and retrograde approach. MATERIALS AND METHODS: We performed an analysis of a single-center series of 279 retroperitoneal laparoscopic adrenalectomies from 1996 to 2010. We compared 172 cases performed with an antegrade approach and 107 with a retrograde approach without dissection of the renal hilum and initial control of the adrenal vein in comparable populations. RESULTS: The operative time was shorter in the group treated with the retrograde technique, 101±51 vs 140±40 minutes, respectively (Student's t test, P<.001). Blood loss was similar in both groups, 85±224 vs 80±126 mL, respectively (P=NS). Hemodynamic instability was defined as the maximal systolic blood pressure minus the minimal systolic blood pressure divided the maximal systolic blood pressure. It was lower in the group who underwent the retrograde technique (32.7 vs 37.6 mL; Student's t test, P=.005) with a lower perioperative consumption of ephedrine (2.2 vs 5.1 mg, P=.004) and atropine (0.09 vs 0.22 mg, P=.026). No difference was found between the 2 groups in the frequency of perioperative complications or postoperative mortality (1 death in each group of causes unrelated to the surgery). CONCLUSION: Retroperitoneal laparoscopic adrenalectomy using a retrograde approach is a safe and reproducible technique. It makes it possible to perform adrenalectomy without dissection of the renal hilum, with a reduction in the operative time. The good hemodynamic stability observed with this technique makes it very attractive for the treatment of pheochromocytoma.

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.

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.

Impact of growth hormone hypersecretion on the adult human kidney.

Acromegaly is most often secondary to a GH-secreting pituitary adenoma with increased Insulin-like Growth Factor type 1 (IGF-1) level. The consequences of GH/IGF-1 hypersecretion reflect the diversity of action of these hormones. The genes of the GH receptor (GHR), IGF-1, IGF-1 receptor (IGF-1R) and IGF-binding proteins (IGF-BP) are physiologically expressed in the adult kidney, suggesting a potential role of the somatotropic axis on renal structure and functions. The expression of these proteins is highly organized and differs according to the anatomical and functional segments of the nephron suggesting different roles of GH and IGF-1 in these segments. In animals, chronic exposure to high doses of GH induces glomerulosclerosis and increases albuminuria. Studies in patients with GH hypersecretion have identified numerous targets of GH/IGF-1 axis on the kidney: 1) an impact on renal filtration with increased glomerular filtration rate (GFR), 2) a structural impact with an increase in kidney weight and glomerular hypertrophy, and 3) a tubular impact leading to hyperphosphatemia, hypercalciuria and antinatriuretic effects. Despite the increased glomerular filtration rate observed in patients with GH hypersecretion, GH is an inefficient treatment for chronic renal failure. GH and IGF-1 seem to be involved in the physiopathology of diabetic nephropathy; this finding offers the possibility of targeting the GH/IGF-1 axis for the prevention and the treatment of diabetic nephropathy.