Gitelman Disease Associated with Growth Hormone Deficiency, Disturbances in Vasopressin Secretion and Empty Sella: A New Hereditary Renal Tubular-Pituitary Syndrome?

Bettinelli, Alberto; Rusconi, Roberto; Ciarmatori, Sonia; Righini, Velella; Zammarchi, Enrico; Donati, Maria Alice; Isimbaldi, Clementina; Bevilacqua, Maurizio; Cesareo, Layla; Tedeschi, Silvana; Garavaglia, Rosanna; Casari, Giorgio

doi:10.1203/00006450-199908000-00017

Cited by 34 publications

(18 citation statements)

References 28 publications

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“…The converse was also true -the urine Ca/creatinine were higher (0.50, 0.54, 0.40) during a water diuresis. Consistent with this implied role of vasopressin, hypocalciuria was an inconsistent finding in two young patients with partial central diabetes insipidus and GS [10].…”

Section: Discussionsupporting

confidence: 49%

Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Ring

Knoers

et al. 2002

Pediatr Nephrol

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A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotransporter; one of these mutations is newly described. Her clinical findings were not typical because of the absence of hypocalciuria in 24-h urine samples, her maximum urine osmolality (U(osm)) was only 802 mosmol/kg H(2)O, and her plasma magnesium (Mg) concentration (P(Mg)) was easily maintained in the normal range with oral Mg supplements for 1 month. In detailed studies, the calcium/creatinine ratio in spot urines with a U(osm) >700 mosmol/kg H(2)O was very low, except during Mg therapy. Renal medullary function did not appear to be compromised because she had a non-urea U(osm)of approximately 600 mosmol/kg H(2)O, reflecting a very high non-urea osmole excretion rate (due to KCl supplements). At age 18 years, her P(Mg) became persistently low despite Mg therapy. We conclude that the clinical criteria for a provisional diagnosis of Gitelman syndrome should be revised. Hypocalciuria may only be evident initially in concentrated spot urine samples. Urine concentrating ability should include an analysis of the non-urea U(osm), especially when patients are taking large KCl supplements.

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Section: Discussionsupporting

confidence: 49%

Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Ring

Knoers

et al. 2002

Pediatr Nephrol

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“…Although clinical cases of isolated GH deficiency as well as improvement of growth rate following administration of indomethacin have been reported in patients with Gitelman's syndrome, the pathogenesis of stunted growth in these hypokalemic disorders is unclear (3,17,31). Few studies have used an experimental rat model of chronic potassium depletion to know the effect of potassium deficiency on the tubular sodium and potassium transport, acid-base balance control, salt sensitivity, and kidney growth (1, 10 -13, 15, 16, 20, 22-26, 33, 34, 36 -38).…”

mentioning

confidence: 99%

Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment

Gil‐Peña¹,

García-López²,

Álvarez-García³

et al. 2009

American Journal of Physiology-Renal Physiology

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of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment. Am J Physiol Renal Physiol 297: F639-F645, 2009. First published July 8, 2009 doi:10.1152/ajprenal.00188.2009.-Hypokalemic tubular disorders may lead to growth retardation which is resistant to growth hormone (GH) treatment. The mechanism of these alterations is unknown. Weaning female rats were grouped (n ϭ 10) in control, potassium-depleted (KD), KD treated with intraperitoneal GH at 3.3 mg ⅐ kg Ϫ1 ⅐ day Ϫ1during the last week (KDGH), and control pair-fed with KD (CPF). After 2 wk, KD rats were growth retarded compared with CPF rats, the osseous front advance (ϮSD) being 67. . GH administration normalized these changes except for the distal chondrocyte height. Quantitative PCR of insulin-like growth factor I (IGF-I), IGF-I receptor, and GH receptor genes in KD growth plates showed downregulation of IGF-I and upregulation of IGF-I receptor mRNAs, without changes in their distribution as analyzed by immunohistochemistry and in situ hybridization. GH did not further modify IGF-I mRNA expression. KD rats had normal hepatic IGF-I mRNA levels and low serum IGF-I values. GH increased liver IGF-I mRNA, but circulating IGF-I levels remained reduced. This study discloses the structural and molecular alterations induced by potassium depletion on the growth plate and shows that the lack of response to GH administration is associated with persistence of the disturbed process of chondrocyte hypertrophy and depressed mRNA expression of local IGF-I in the growth plate.tubulopathies; chondrocyte; cartilage GROWTH RETARDATION IS FREQUENTLY found in primary hypokalemic tubular disorders (32). Potential pathogenic factors of growth impairment in these tubulopathies include maintained metabolic acidosis, polyuria with decreased food intake and repeated dehydration episodes, disturbed bone mineralization, sodium deficit, and potassium depletion. In children with renal tubular acidosis, growth retardation is common and is ameliorated or reversed after sustained correction of metabolic acidosis (29). Metabolic acidosis disturbs normal growth through various mechanisms such as the stimulation of protein catabolism (18), interference with growth hormone (GH) action (21), and the alteration of the structure and dynamics of growth cartilage (5). In hypokalemic tubulopathies associated with alkalosis, Bartter's or Gitelman's syndromes, the adverse effect on growth is not well documented and the response of growth to treatment is rather unpredictable. Growth impairment is frequently described in Bartter's syndrome (22). Gitelman's syndrome, traditionally considered as asymptomatic or responsible for mild clinical manifestations (9), has been reported to be accompanied by short stature in over 30% of children (8).Although clinical cases of isolated GH deficiency as well as improvement of growth rate following administration of indomethacin have been reported in patients with Gitelman's syndrome, the...

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“…MR revealed an empty sella in these patients. Therefore, these cases represent a new phenotype not previously described in Gitelman disease, and the entity may be considered a new complex hereditary renal tubular-pituitary syndrome [11]. However, cranial and pituitary MR of our patient was normal.…”

Section: Discussionmentioning

confidence: 39%

A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis

et al. 2010

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Bartter syndrome is a rare autosomal recessive, salt-losing disorder characterized by hypokalemic hypochloremic metabolic alkalosis. A 10-year-old boy had severe growth retardation (height standard deviation score -8.15). He had a thin, triangular face, prominent ears and forehead, and big eyes. Megacystis, bilateral hydroureteronephrosis, and residual urine were detected in ultrasonography, but there was no vesicoureteral reflux. Lumbosacral magnetic resonance (MR) showed posterior disc bulging at L4-5. Serum sodium and chloride levels were normal, but mild hypokalemia was overlooked initially. During follow-up, hypokalemic hypochloremic metabolic alkalosis developed, with high urinary chloride and potassium excretion (52 and 43 mEq/L, respectively). The patient, with renal salt loss, was thought to have classic Bartter syndrome due to absence of nephrocalcinosis, presence of persistent hypercalciuria and sensorineural deafness, and presence of relatively mild clinical and laboratory findings, except polyuria initially. The child was treated with indomethacin, spironolactone, and oral potassium in addition to growth hormone (GH). During treatment, he had considerable increase in weight and height compared with the period of GH therapy only. We present this case because, although growth retardation is a major feature of Bartter syndrome, associated GH deficiency is rarely reported in the literature. Diagnosis of Bartter syndrome was made later, as our patient was followed for megacystis and megaureter secondary to the neurogenic bladder and GH deficiency initially; and proteinuria associated with focal segmental glomerulosclerosis responded to treatment for Bartter syndrome.

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Gitelman Disease Associated with Growth Hormone Deficiency, Disturbances in Vasopressin Secretion and Empty Sella: A New Hereditary Renal Tubular-Pituitary Syndrome?

Cited by 34 publications

References 28 publications

Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Reevaluation of the criteria for the clinical diagnosis of Gitelman syndrome

Alterations of growth plate and abnormal insulin-like growth factor I metabolism in growth-retarded hypokalemic rats: effect of growth hormone treatment

A patient with Bartter syndrome accompanying severe growth hormone deficiency and focal segmental glomerulosclerosis

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