The Phenotypic Variability Associated with Hepatocyte Nuclear Factor 1B Genetic Defects Poses Challenges in Both Diagnosis and Therapy.

The evolving landscape of clinical genetics is becoming increasingly relevant in the field of nephrology. HNF1B-associated renal disease presents with a diverse array of renal and extrarenal manifestations, prominently featuring cystic kidney disease and diabetes mellitus. For the genetic analyses, whole exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were performed. Bioinformatics analysis was performed with Ingenuity Clinical Insights software (Qiagen). The patient's electronic record was utilized after receiving informed consent. In this report, we present seven cases of HNF1B-associated kidney disease, each featuring distinct genetic abnormalities and displaying diverse extrarenal manifestations. Over 12 years, the mean decline in eGFR averaged -2.22 ± 0.7 mL/min/1.73 m2. Diabetes mellitus was present in five patients, kidney dysplastic lesions in six patients, pancreatic dysplasia, hypomagnesemia and abnormal liver function tests in three patients each. This case series emphasizes the phenotypic variability and the fast decline in kidney function associated with HNF-1B-related disease. Additionally, it underscores that complex clinical presentations may have a retrospectively straightforward explanation through the use of diverse genetic analytical tools.

Human placental growth hormone in normal and abnormal fetal growth.

Human placental growth hormone (PGH), encoded by the growth hormone (GH) variant gene on chromosome 17, is expressed in the syncytiotrophoblast and extravillous cytotrophoblast layers of the human placenta. Its maternal serum levels increase throughout pregnancy, and gradually replaces the pulsatile secreted pituitary GH. PGH is also detectable in cord blood and in the amniotic fluid. This placental-origin hormone stimulates glyconeogenesis, lipolysis and anabolism in maternal organs, and influences fetal growth, placental development and maternal adaptation to pregnancy. The majority of these actions are performed indirectly by regulating maternal insulin-like growth factor-I levels, while the extravillous trophoblast involvement indicates a direct effect on placental development, as it stimulates trophoblast invasiveness and function via a potential combination of autocrine and paracrine mechanisms. The current review focuses on the role of PGH in fetal growth. In addition, the association of PGH alterations in maternal circulation and placental expression in pregnancy complications associated with abnormal fetal growth is briefly reviewed.

A complicated case of primary hypophysitis with bilateral intracavernous carotid artery occlusion.

UNLABELLED: Primary hypophysitis (PH) is a rare clinical entity characterized by inflammatory infiltration of the pituitary gland with various degrees of pituitary dysfunction. OBJECTIVE: To present a complicated case of aggressive PH with bilateral cavernous sinuses infiltration, successfully treated with azathioprine after failure of corticosteroid treatment. METHODS AND RESULTS: A 48-year-old woman presented with episodes of recurrent headache and progressively worsening muscle weakness. Magnetic resonance imaging (MRI) identified an intrasellar pituitary lesion with thickened pituitary stalk extending to the cavernous sinuses and causing asymptomatic occlusion of both internal carotid arteries (ICAs). Hormonal investigation showed severe anterior pituitary deficiency. The diagnosis of PH, and more specifically of lymphocytic hypophysitis (LYH), was suspected and glucocorticoid treatment was initiated. Because of the patient's susceptibility to infections, the attempt to gradually reduce glucocorticoid dosage induced a relapse of PH. Immunosuppressive therapy with azathioprine was administered. Significant pituitary mass reduction with regression of the inflammation to the cavernous sinuses was documented. At follow-up the pituitary function was normal, while the patient was on the minimum dose of azathioprine. Thereafter, azathioprine was discontinued without any clinical/biochemical or radiological evidence of PH except for the permanent ICA occlusion. CONCLUSIONS: Despite its rarity, PH should be included in the differential diagnosis of pituitary masses and involvement of ICAs occlusion should not be underestimated. Azathioprine, applied as an alternative treatment, was shown to result in remarkable PH improvement.